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1.
氟苯尼考在欧洲鳗鲡体内的药物代谢动力学的研究   总被引:11,自引:0,他引:11  
应用反相高效液相色谱法对口灌和肌肉注射氟苯尼考在欧洲鳗鲡(Anguilla anguilla)体内的代谢规律进行了研究.按100 mg·kg-1口灌给药后血浆、肌肉、肝脏、肾脏中氟苯尼考浓度的达峰时间分别为2h、6h、0.5h、1h,以后开始缓慢下降,给药2d后血浆、肌肉、肝脏、肾脏中的氟苯尼考浓度分别为4.209μg·mL-1、0.792μg·g-1、0.493μg·g-1、1.448μg·g-1,给药3d后血浆中的氟苯尼考浓度分别为0.0836μg·mL-1,肌肉、肝脏、肾脏中的氟苯尼考浓度均未检出;按100mg·kg-1肌肉注射给药后血浆中氟苯尼考浓度达峰时间为0.5h,以后开始缓慢下降,给药5d后血浆中的氟苯尼考浓度为0.1151μg·mL-1,给药10d后血浆中的氟苯尼考浓度未检出.口灌氟苯尼考在欧洲鳗鲡体内血浆、肌肉、肝脏、肾脏中分布可用开放性二室模型来描述,口灌给药的血浆、肌肉、肝脏、肾脏中的消除半衰期(T1/2β)分别为27.939h、18.844h、11.83h、36.87h;肌肉注射氟苯尼考在欧洲鳗鲡体内血浆、肌肉、肝脏、肾脏中分布可用开放性一室模型来描述,肌肉注射给药的血浆中的消除半衰期(T1/2β)为37.52h.  相似文献   

2.
硫酸新霉素在吉富罗非鱼体内的药代动力学及休药期   总被引:1,自引:0,他引:1  
在实验水温(28±2)℃条件下,按25 mg·kg-1 的剂量对吉富罗非鱼(Genetically improved farmed tilapia,GIFT)单次口灌给药后,采用UPLC-MS/MS法测定吉富罗非鱼组织中的药物水平,研究硫酸新霉素在吉富罗非鱼体内的药代动力学及消除规律.结果表明,血药浓度时间数据符合一级吸收二室开放模型,药物在血浆中达峰时间Tmax、血药浓度高峰Cmax和消除半衰期T1/2β分别为1.299 h、16.138 μg·mL-1 和25.776 4 h.药物消除速度由快到慢依次为:肌肉、肝脏、肾脏,消除半衰期T1/2β分别为31.802 h、34.917 h、45.175 h.选取吉富罗非鱼可食性肌肉组织作为残留检测靶组织,参考中华人民共和国第235号公告中对禽肌肉MRL规定,以0.5 mg·kg-1为残留限量,建议休药期不低于6 d.  相似文献   

3.
陈琛  卢彤岩  王荻  李绍戊 《鲑鳟渔业》2011,(4):25-28,58
实验水温为15±2℃,金鳟(Oncorhynchus mykiss)(平均体质量100±10g)单剂量肌肉注射30.0 mg/kg诺氟沙星后,应用高效液相色谱(HPCL)法于0.15,0.25,0.5,0.75,1,1.5,2,4,6,8,12,24,48,72 h测定了鱼血浆、肝脏和肾脏组织中药物的浓度,研究了诺氟沙星在金鳟组织中的分布及药物动力学规律。结果表明,诺氟沙星在金鳟体内吸收分布迅速,符合药物动力学一级吸收二室开放模型,但消除缓慢。诺氟沙星在金鳟血浆、肝脏和肾脏中的主要动力学参数如下:分布半衰期(T1/2α)分别为0.866、1.985、0.388h;消除半衰期(T1/2β)分别为31.369、36.402、30.975h;药时曲线下面积(AUC)分别为:308.005μg/mL.h、622.721μg/g.h、794.362μg/g.h。  相似文献   

4.
水温(28±2)℃时,按20mg/kg的剂量给平均体质量(500±10)g的鳜鱼单次口服乳酸诺氟沙星,服药后0.5、1、2、3、4、6、8、12、24、48、72、96h,分别测定鳜鱼血浆、肌肉、肝脏和肾脏中的药物含量,采用非房室模型分析药物在鳜鱼体内的代谢消除规律。结果显示,乳酸诺氟沙星在鳜鱼血浆、肌肉、肝脏、肾脏中的达峰时间分别为4.333、6、3、5h,达峰质量浓度分别为3.625、2.39、33.089、19.375mg/L,各组织中肝脏吸收的药物含量最高,其次是肾脏、血浆和肌肉;乳酸诺氟沙星在鳜鱼血浆、肌肉、肝脏、肾脏中的消除半衰期分别为42.589、131.652、16.830、30.558h,药物在肝脏中消除速度最快,而在肌肉中消除最慢。以肌肉中药物残留限量为50μg/kg计,建议单次投喂乳酸诺氟沙星的休药期不低于24d。  相似文献   

5.
在试验水温(25±1)℃时,按100μg·L-1的剂量给欧洲鳗鲡药浴溴氰菊酯36h后,采用气相色谱法测定血浆和肌肉中的药物浓度,研究了溴氰菊酯在欧洲鳗鲡体内的代谢及消除规律.采用DAS自动化药动学分析程序对数据进行分析.结果表明:欧洲鳗鲡血浆和肌肉中溴氰菊酯经时过程均符合一级吸收一室开放模型,血浆中主要药动学参数为:T1/2k为148.296h,Cmax为18.446μg·L-1,Tmax为14.7h.肌肉中主要药动学参数为:T1/2k为386.912h,Cmax为44.291μg·kg-1,Tmax为49.6h.肌肉作为可食性组织,且消除较慢,因此选取肌肉组织作为残留检测的靶组织,以10μg·kg-1为最高残留限量,在本试验条件下,建议休药期不低于9d.  相似文献   

6.
应用反相高效液相色谱法,研究药浴给药条件下,恩诺沙星及其代谢产物环丙沙星在欧洲鳗鲡体内的药代动力学.按10mg·L-1药浴给药后,恩诺沙星在欧洲鳗体内各组织器官中分布可用开放性二室模型来描述.血浆、肌肉、肝脏和肾脏中恩诺沙星达峰时间分别为44.27h、42.74h、50.69h、95.80h,以后开始缓慢下降,血浆、肌肉、肝脏和肾脏中代谢产物环丙沙星达峰时间分别为48.89h、55.34h、54.64h、100.0h.给药3个月后血浆、肌肉、肝脏和肾脏中的恩诺沙星浓度分别为0.0844μg·mL-1、0.09959μg·g-1、0.01242μg·g-1、3.7164u·g-1;恩诺沙星在血浆、肌肉、肝脏和肾脏中的消除半衰期(T1/2β)分别为908.07h、901.24h、59.32h、767.81h.鉴于恩诺沙星和其代谢产物环丙沙星在欧洲鳗鲡体内消除较慢,建议养成阶段不使用此药.  相似文献   

7.
多次口灌呋喃唑酮在草鱼体内残留研究   总被引:1,自引:0,他引:1  
报道了多次口灌呋喃唑酮(60 mg/kg,连续3 d,每天1次)在草鱼体内血浆、肌肉、肝脏和肾脏中的消除与残留研究。采用高效液相色谱法(HPLC)检测用药后不同时间各组织中药物浓度,M ILLEMNIUM32工作站处理原始数据,MCPKP药代动力学软件处理药时数据。结果表明:多次口灌呋喃唑酮在草鱼体内的药时数据符合一级速率吸收一室开放模型,其主要药动学参数为:AUC 2.3182μg.h/m l,Cmax 0.850μg/m l,Ka 0.5515 h-1,K 0.0936 h-1,T1/2ka1.2565h,T1/2k7.4308h,Tp 2.8732 h,药物在血浆、肌肉、肝脏、肾脏中消除时间分别为:72 h、15 d、20 d、20 d。  相似文献   

8.
在水温(28±2)℃、盐度28条件下,采用30mg/kg的剂量口灌法,用HPLC-MS/MS检测研究了盐酸氯苯胍在体质量为(350.15±5.18)g的眼斑拟石首鱼体内的药代动力学和残留消除规律。结果显示,单剂量口灌给药后,眼斑拟石首鱼血浆中盐酸氯苯胍的药时数据符合一级吸收二室模型,药物在血浆中的达峰时间、血药质量浓度峰值、药时曲线下面积和消除半衰期分别为2.39h、958.78μg/L、33 247.57μg/(L·h)和19.24h;盐酸氯苯胍在肌肉、肝脏和肾脏的血药含量峰值分别为156.72、227.68μg/kg和553.44μg/kg,达峰时间分别为2.0、1.5、2.0h;药时曲线下面积分别4664.04、4897.74、17 228.19μg/(kg·h);消除半衰期分别为19.68、24.33、22.81h。按30mg/kg剂量连续5d口灌给药后,鱼血浆、肌肉、肝脏、肾脏中的药物消除半衰期(t1/2)分别为24.46、35.39、39.60、33.94h。若以10μg/kg为最高残留限量,肌肉作为食用靶组织,在本试验条件下,建议休药期不少于7d。  相似文献   

9.
利用高效液相色谱法分别测定了单次和多次混饲口灌大菱鲆诺氟沙星(NFLX)后鱼体主要组织中的NFLX含量。通过MCP-KP药动学程序对NFLX在大菱鲆体内的药代动力学及残留消除规律进行了分析研究。结果表明,以30mg/kg的剂量单次混饲口灌大菱鲆,NFLX在大菱鲆体内的达峰时间(Tmax)为2h,血、鳃、肾脏、肝脏、肌肉的达峰浓度(Cmax)分别为:8.365、7.519、1.871、6.485和4.060μg/g;NFLX在组织中的消除半衰期(T1/2)由小到大依次为:肝脏8.18h<肌肉12.39h<鳃丝15.29h<血液23.22h<肾脏23.25h。连续5d以30mg/kg的剂量混饲口灌大菱鲆,消除半衰期(T1/2)由小到大依次为:肌肉74.88h<血液98.16h<肝脏186.43h<鳃192.12h<肾脏200.45h。以上研究表明,诺氟沙星在大菱鲆体内的吸收较为迅速,有利于疾病的预防和治疗用药。在组织中以肾脏中的残留最为显著。使用诺氟沙星进行大菱鲆疾病的预防和治疗时,至少停药30d后方可上市销售。  相似文献   

10.
在14±2℃水温条件下,连续5d对红鳍东方鲍口灌剂量为100mg/kg的土霉素,采用高效液相色谱法测定了停药后血清、肌肉、肝脏组织中的药物含量、消除速率常数和消除半衰期,提出了该温度下的休药期。研究表明,在停药2d后红鳍东方鲍血清和肌肉中的药物浓度达到峰值,分别为1.092μg/ml和0.806μg/g;停药3d后肝脏内土霉素浓度达到峰值1.229μg/g,土霉素在血清、肌肉和肝脏中的消除半衰期分别为23.8、22.4和26.8d;土霉素在红鳍东方纯肌肉组织中降到0.1μg/g残留限量的时间为58d,降到0.05μg/g残留限量的时间为81d。  相似文献   

11.
The environmental processes associated with variability in the catch rates of bigeye tuna in the Atlantic Ocean are largely unexplored. This study used generalized additive models (GAMs) fitted to Taiwanese longline fishery data from 1990 to 2009 and investigated the association between environmental variables and catch rates to identify the processes influencing bigeye tuna distribution in the Atlantic Ocean. The present findings reveal that the year (temporal factor), latitude and longitude (spatial factors), and major regular longline target species of albacore catches are significant for the standardization of bigeye tuna catch rates in the Atlantic Ocean. The standardized catch rates and distribution of bigeye tuna were found to be related to environmental and climatic variation. The model selection processes showed that the selected GAMs explained 70% of the cumulative deviance in the entire Atlantic Ocean. Regarding environmental factors, the depth of the 20 degree isotherm (D20) substantially contributed to the explained deviance; other important factors were sea surface temperature (SST) and sea surface height deviation (SSHD). The potential fishing grounds were observed with SSTs of 22–28°C, a D20 shallower than 150 m and negative SSHDs in the Atlantic Ocean. The higher predicted catch rates were increased in the positive northern tropical Atlantic and negative North Atlantic Oscillation events with a higher SST and shallow D20, suggesting that climatic oscillations affect the population abundance and distribution of bigeye tuna.  相似文献   

12.
In this experiment, a feeding trial was performed to determine the effects of fructooligosaccharide (FOS) on growth performance, digestive enzyme activity and immune response of Japanese sea bass, Lateolabrax japonicus juveniles (initial weight 38.3 ± 0.5 g), and the fish were examined following feeding with six levels of FOS (0, 0.5, 1, 2, 4 and 6 g/kg) for 28 days. Significant enhancement of weight gain (WG) and specific growth rate (SGR) was found in fish fed 1 g/kg FOS incorporated diets (p < .05), while the feed conversion ratio (FCR) in the 1, 2 g/kg FOS groups reduced significantly compared with the control (p < .05). Besides, the crude lipid in the 4, 6 g/kg FOS groups increased significantly compared with the control (p < .05). On the other hand, the erepsin and lipase activities significantly elevated in intestine of fish fed 2 g/kg FOS (p < .05) and the lysozyme activity in serum of fish fed 2 g/kg FOS were significantly higher than that in the control (p < .05). Moreover, the alkaline phosphatase activities in serum of fish fed 0.5, 1, 2 g/kg FOS were significantly higher than in control (p < .05). Regression analysis showed that the relationships between dietary FOS levels and either SGR, FCR, erepsin or lysozyme activities were best expressed by regression equations, and the optimal inclusion levels are 1.37, 1.80, 3.06, 3.11, 1.93 and 1.80 g/kg for SGR, FCR, erepsin, lipase, lysozyme and total superoxide dismutase activities, respectively. Overall, this study revealed that FOS incorporated diets could beneficial for L. japonicus culture in terms of increasing the growth, digestion and immune activities. Under the present experimental condition, the optimal supplementary level of FOS in the diet of L. japonicus is 1–3 g/kg.  相似文献   

13.
Protein and amino acid composition of the mantle of juvenile O ctopus vulgaris (Cuvier, 1797) during fasting for 27 days were determined. Average protein content of octopus mantle was of 711.19 ± 46.80 g kg?1 DW, and it decreased with increasing fasting days. The non‐essential amino acids content was higher (486.18 ± 11.08 g kg?1 protein) than essential amino acids (425.82 ± 9.15 g kg?1 protein) at the start of the experiment (unstarved animals). The results suggest that the amino acid profile of the mantle where the most abundant amino acids are Arg, His, Lys, Gly, Leu and Pro could indicate a prolonged fasting condition (>20 days) or poor nutrition of O . vulgaris. This study supports the idea of using mantle for metabolic needs of starved O . vulgaris suggesting that the degradation pathway of amino acids to pyruvate and tricarboxylic acid cycle intermediates was favoured contrary to the degradation pathway of ketogenic amino acids. Special considerations should be taken concerning Thr, Ile, Ser, Ala, Asx (Asp, Asn), Glx (Glu, Gln) (because of their fast intake) and Lys and His (due to their stable contents) during a prolonged period of fasting.  相似文献   

14.
Plasma estradiol-17 (E2), testosterone (T), 17,20-dihydroxy-4-pregnen-3-one (DHP) and 17,20,21-tri-hydroxy-4-pregnen-3-one (20-S) levels were measured by radioimmunoassay (RIA) in white perch (Morone americana) and white bass (M. chrysops) that were induced to undergo final oocyte maturation (FOM) with human chorionic gonadotropin (hCG). Plasma DHP levels increased in females of both species in association with oocyte germinal vesicle migration (GVM) and germinal vesicle breakdown (GVBD) and decreased thereafter. Plasma 20-S levels also increased with oocyte GVM in white bass, but were several-fold lower than DHP levels. Circulating E2 and T levels were greatest during GVM and GVBD in both species and decreased to low levels during oocyte hydration and ovulation. Follicles from white perch and white bass which received a priming injection of hCG in vivo, produced both DHP and 20-S in vitro after exposure to hCG and their oocytes underwent GVBD. Ovarian incubates from unprimed fish of either species produced only E2 and T and their oocytes did not complete GVBD. Oocytes from unprimed bass, but not perch, matured when follicles were exposed to hCG in vitro. Both trilostane and cycloheximide blocked in vitro production of DHP and 20-S and oocyte GVBD by white perch follices. DHP and 20-S were equipotent inducers of FOM in the GVBD bioassay. None of several other structurally-related steroids tested were effective within a physiological range of concentrations. These results indicate a role for DHP and 20-S in the control of FOM in white perch and white bass.  相似文献   

15.
Changes in heart rate, ventilatory activity and oxygen consumption were determined in trout (Salmo gairdneri) and brown bullhead catfish (Ictalurus nebulosus) during exposure to a steadily increasing concentration of waterborne cyanide selected to produce death in 8–9 hours for each species. The lethal cyanide concentration for the bullheads was an order of magnitude higher than for trout. Trout developed an immediate and gradually increasing bradycardia throughout the exposure period. Cyanide produced tachycardia in the bullhead followed by a gradual onset of bradycardia as the concentration of cyanide was raised. Pericardial injection of atropine (a muscarinic cholinergic antagonist) indicated that bradycardia in the trout was due initially to increased vagal tone but later due to the direct effect of cyanide on the heart. Hyperventilation in the trout persisted throughout the exposure period, although the rate and amplitude fluctuated and was variable between individual fish. During the last hour of exposure (highest cyanide concentration), ventilation was characterized by rapid, shallow breaths followed by a sudden respiratory arrest. The bullheads exhibited hyperventilation during the first 3 hours of exposure followed by a gradual, linear drop in ventilation rate and amplitude until death occurred. Cardiac and ventilatory responses in both species were attributed to stimulation of central and peripheral chemoreceptors by cyanide. Evidence is presented which suggests the initial response in the bullheads was due, at least in part, to gustatory stimulation by the cyanide. Oxygen consumption of the trout remained above pre-exposure levels for the majority of the test period. Oxygen consumption in the bullhead paralleled the changes in heart and ventilatory rates. Whole-body lactate levels of fingerlings of both species during cyanide exposure were measured to estimate the extent of anaerobiosis. Whole-body lactate levels were much greater in the bullheads than the trout, indicating a higher capacity for anaerobiosis, possibly due to a greater fuel supply. Overall, the trout responded to cyanide in a manner similar to that produced by environmental hypoxia whereas the bullheads experienced a gustatory stimulus which masked the hypoxia-like response.  相似文献   

16.
This study brings an integrated analysis about the relationship between water deterioration and its physiological consequences in live fish transport. The analysis was focused on the transport water and its deterioration, and physiological challenges imposed on the fish. Usual commercial handling procedures employed to mitigate fish stress during transport were discussed. Future topics of research for the establishment of safer fish transport protocols were proposed. Transport was classified into short (≤8 h) or long transport (>8 h). The main issue in short transports should be the prevention of water pH reduction, while in long transports it is the increase in ammonia. Plasma cortisol is the most employed marker for stress and is acutely elevated upon short episodes of transport, but remains elevated even in long‐transport events. Plasma glucose is perhaps a better marker for handling stress. Plasma lactate, pH, osmolality CO2 and ions should be more often evaluated. Plasma Na+ and Cl are very useful markers of acidosis, due to their respective exchange for H+ and , for acid–base regulation. The establishment of species‐specific transport protocols should be preceded by such combined analyses of water and physiological parameters.  相似文献   

17.
Abalone populations have declined worldwide, generating interest in enhancement using hatchery‐reared individuals. In many cases, such restoration efforts have met with limited success due to high predator‐induced mortality rates. Furthermore, the mortality rates of outplanted hatchery abalone are often considerably higher than for wild individuals. This study uses northern abalone (Haliotis kamtschatkana) as a case study to determine whether hatchery‐reared abalone behave differently than their wild counterparts. In the field, outplanted hatchery‐reared abalone were significantly less responsive than wild abalone, in terms of number of abalone responding and intensity of response, to nearby movement and to physical contact with an inert probe. Also, when encountering a cue to which all abalone responded (a seastar predator), hatchery‐reared individuals remained subdued. Anti‐predator behavioural deficits in hatchery‐reared abalone were more pronounced in 4‐year‐old individuals than in 1‐year‐old individuals, suggesting an influence of either age or amount of time spent in the hatchery environment. These behavioural differences are expected to increase the vulnerability of hatchery‐reared abalone to predators, and are likely a major cause of their elevated predator‐induced mortality when outplanted.  相似文献   

18.
The toxic effects of Cd2+ on Ca2+ influx kinetics in developing tilapia (Oreochromis mossambicus) larvae were evaluated. Addition of 20 µg l-1 of Cd2+ to the environment of 0 and 3 day-old larvae competitively inhibited the Ca2+ uptake within 4h resulting in a great increase in Km values for Ca2+ influx (19.3 and 17.4 fold, respectively) as compared with their respective controls. Consequently, the actual Ca2+ influx of larvae in solutions of 0.2 mM Ca2+ are suppressed by 32–45%. Also, 3 day-old larvae were more sensitive to internally accumulated Cd2+ than 0 day-old larvae. Although the Ca2+ influx in 0 and 3 day-old larvae may be restored to the levels of their respective controls with 24h of being transferred to a 20 µg l-1 Cd2+ solution, total body Ca2+ content was significantly reduced in 3 day-old larvae. Increased Ca2+ uptake efficiency ensures sufficient Ca2+ for normal growth. However, rapid increase in Ca2+ influx after hatching also leads to higher Cd2+ uptake. Exposure to Cd2+ will lead to a drop in body Ca2+ content resulting in retardation of larval growth. Therefore, we conclude that if Ca2+ uptake is interfered with at this critical stage of development, larvae will not be able to maintain normal levels of body Ca2+ and will show signs of Cd2+ poisoning.  相似文献   

19.
Migratory dynamics of stream-spawning longnose gar (Lepisosteus osseus)   总被引:1,自引:1,他引:0  
Abstract– Literature evidence suggests that lake-dwelling longnose gar (Lepisosteus osseus) enter tributary streams to spawn, Until the present study, the dynamics of this breeding migration had never been investigated quantitatively. During the summers of 1991 and 1992, longnose gar were captured as they entered Weaubleau Creek, Missouri, a tributary of Harry S. Truman Reservoir. The in-stream spawning migration began in early April and ended in late May, and was positively correlated with stream flow and water level, and negatively correlated with water temperature. In-stream residence times ranged from 15 to 94 days, with males exhibiting longer residence times than females. Once in-stream, longnose gar travelled as far as 10 km upstream and occupied certain pools at greater relative frequencies. Although the reason for this preferential utilization is not completely understood, it may relate to pool depth and riffle proximity. Longnose gar disperse from the spawning stream great distances, with gar captured in Weaubleau Creek being recaptured up to 48 km away. This information should provide fisheries biologists the means to consider the reproductive ecology of this species in their conservation and management decisions.  相似文献   

20.
The desaturation and elongation of [1-14C]18:3n-3 was investigated in hepatocytes of the tropical warm freshwater species, zebrafish (Danio rerio) and Nile tilapia (Oreochromis niloticus). The hepatocyte fatty acid desaturation/elongation pathway was assayed before and after the fish were fed two experimental diets, a control diet containing fish oil (FO) and a diet containing vegetable oil (VO; a blend of olive, linseed and high oleic acid sunflower oils) for 10 weeks. The VO diet was formulated to provide 1% each of 18:2n-6 and 18:3n-3, and so satisfy the possible EFA requirements of zebrafish and tilapia. At the end of the dietary trial, the lipid and fatty acid composition was determined in whole zebrafish, and liver, white muscle and brain of tilapia. Both zebrafish and tilapia expressed a hepatocyte fatty acid desaturation/elongation pattern consistent with them being freshwater and planktonivorous fish. The data also showed that hepatic fatty acid desaturation/elongation was nutritionally regulated with the activities being higher in fish fed the VO diet compared to fish fed the FO diet. In zebrafish, the main effect of the VO diet was increased fatty acid Δ6 desaturase activity resulting in the production of significantly more 18:4n-3 compared to fish fed the FO diet. In tilapia, all activities in the pathway were greater in fish fed the VO diet resulting in increased amounts of all fatty acids in the pathway, but primarily eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). However, the fatty acid compositional data indicated that despite increased activity, desaturation of 18:3n-3 was insufficient to maintain tissue proportions of EPA and DHA in fish fed the VO diet at the same level as in fish fed the FO diet. Practically, these results indicate that manipulation of tilapia diets in commercial culture in response to the declining global fish oil market would have important consequences for fish fatty acid composition and the health of consumers. Scientifically, zebrafish and tilapia, both the subject of active genome mapping projects, could be useful models for studies of lipid and fatty acid metabolism at a molecular biological and genetic level. This revised version was published online in August 2006 with corrections to the Cover Date.  相似文献   

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