全文获取类型
收费全文 | 616篇 |
免费 | 83篇 |
国内免费 | 71篇 |
专业分类
农学 | 1篇 |
1篇 | |
综合类 | 127篇 |
农作物 | 8篇 |
水产渔业 | 68篇 |
畜牧兽医 | 558篇 |
植物保护 | 7篇 |
出版年
2023年 | 7篇 |
2022年 | 13篇 |
2021年 | 17篇 |
2020年 | 65篇 |
2019年 | 53篇 |
2018年 | 53篇 |
2017年 | 20篇 |
2016年 | 27篇 |
2015年 | 17篇 |
2014年 | 28篇 |
2013年 | 22篇 |
2012年 | 33篇 |
2011年 | 25篇 |
2010年 | 27篇 |
2009年 | 19篇 |
2008年 | 32篇 |
2007年 | 37篇 |
2006年 | 30篇 |
2005年 | 21篇 |
2004年 | 29篇 |
2003年 | 26篇 |
2002年 | 21篇 |
2001年 | 20篇 |
2000年 | 15篇 |
1999年 | 17篇 |
1998年 | 12篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 11篇 |
1994年 | 8篇 |
1993年 | 8篇 |
1992年 | 9篇 |
1991年 | 3篇 |
1990年 | 7篇 |
1989年 | 10篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有770条查询结果,搜索用时 109 毫秒
1.
Shuang Liu Taocui Zhang Huifang Sun Lisha Lin Na Gao Weili Wang Sujuan Li Jinhua Zhao 《Marine drugs》2021,19(4)
dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber Holothuria fuscopunctata. As a selective inhibitor of intrinsic Xase (iXase), preclinical study showed it was a promising anticoagulant candidate without obvious bleeding risk. In this work, two bioanalytical methods based on the anti-iXase and activated partial thromboplastin time (APTT) prolongation activities were established and validated to determine dHG-5 concentrations in plasma and urine samples. After single subcutaneous administration of dHG-5 at 5, 9, and 16.2 mg/kg to rats, the time to peak concentration (Tmax) was at about 1 h, and the peak concentration (Cmax) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(T1/2β) was also about 1 h and dHG-5 could be almost completely absorbed after s.c. administration. Additionally, the pharmacodynamics of dHG-5 was positively correlated with its pharmacokinetics, as determined by rat plasma APTT and anti-iXase method, respectively. dHG-5 was mainly excreted by urine as the unchanged parent drug and about 60% was excreted within 48 h. The results suggested that dHG-5 could be almost completely absorbed after subcutaneous injection and the pharmacokinetics of dHG-5 are predictable. Studying pharmacokinetics of dHG-5 could provide valuable information for future clinical studies. 相似文献
2.
Pharmacokinetics of xylazine after 2-, 4-, and 6-hr durations of continuous rate infusions in horses
Klaus Hopster Lawrence R. Soma Xiaoqing Li Charlotte Hopster-Iversen Raymond C. Boston Bernd Driessen 《Journal of veterinary pharmacology and therapeutics》2020,43(6):557-564
Intravenous (i.v.) bolus administration of xylazine (XYL) (0.5 mg/kg) immediately followed by a continuous rate infusion (CRI) of 1 mg kg−1 hr−1 for 2, 4, and 6 hr produced immediate sedation, which lasted throughout the duration of the CRI. Heart rate decreased and blood pressure increased significantly (p > .05) in all horses during the first 15 min of infusion, both returned to and then remained at baseline during the duration of the infusion. Compartmental models were used to investigate the pharmacokinetics of XYL administration. Plasma concentration–time curves following bolus and CRI were best described by a one-compartment model. No differences were found between pharmacokinetic estimates of the CRIs for the fractional elimination rate constant (Ke), half-life (t1/2e), volume of distribution (Vd), and clearance (Cl). Median and range were 0.42 (0.15–0.97)/hr, 1.68 (0.87–4.52) hr, 5.85 (2.10–19.34) L/kg, and 28.7 (19.6–39.5) ml min−1 kg−1, respectively. Significant differences were seen for area under the curve ( ) (p < .0002) and maximum concentration (Cmax) (p < .04). This indicates that with increasing duration of infusion, XYL may not accumulate in a clinically relevant way and hence no adjustments are required in a longer XYL CRI to maintain a constant level of sedation and a rapid recovery. 相似文献
3.
Mariana Ballent Maria Laura Mat Paula Dominguez Guillermo Virkel Melanie Albrich Anne Lespine Carlos Lanusse Adrian Luis Lifschitz 《Journal of veterinary pharmacology and therapeutics》2019,42(2):189-196
The aim of the current study was to evaluate the in vivo pharmacokinetic of ivermectin (IVM) after the administration of a long‐acting (LA) formulation to sheep and its impact on potential drug‐drug interactions. The work included the evaluation of the comparative plasma profiles of IVM administered at a single therapeutic dose (200 μg/kg) and as LA formulation at 630 μg/kg. Additionally, IVM was measured in different gastrointestinal tissues at 15 days posttreatment with both IVM formulations. The impact of the long‐lasting and enhanced IVM exposure on the disposition kinetics of abamectin (ABM) was also assessed. Plasma (IVM and ABM) and gastrointestinal (IVM) concentrations were analyzed by HPLC with fluorescent detection. In plasma, the calculated Cmax and AUC0‐t values of the IVM‐LA formulation were 1.47‐ and 3.35‐fold higher compared with IVM 1% formulation, respectively. The T1/2ab and Tmax collected after administration of the LA formulation were 2‐ and 3.5‐fold longer than those observed after administration of IVM 1% formulation, respectively. Significantly higher IVM concentrations were measured in the intestine mucosal tissues and luminal contents with the LA formulation, and in the liver, the increase was 7‐fold higher than conventional formulation. There was no drug interaction between IVM and ABM after the single administration of ABM at 15 days post‐administration of the IVM LA formulation. The characterization of the kinetic behavior of the LA formulation to sheep and its potential influence on drug‐drug interactions is a further contribution to the field. 相似文献
4.
Sridhar Veluvolu Jennifer L. Willcox Katherine A. Skorupski Sami Al-Nadaf Robert Rebhun Luke Wittenburg 《Veterinary and comparative oncology》2023,21(1):20-27
Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200–250 mg/m2 over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h−1; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200–250 mg/m2. 相似文献
5.
Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon) 下载免费PDF全文
Christopher Scala Amélie Marsot Marie‐Josée Limoges Yann Locatelli Nicolas Simon Jean‐Claude Alvarez 《Veterinary anaesthesia and analgesia》2015,42(2):165-172
ObjectiveTo assess the population pharmacokinetics of methadone in deer.Study designProspective non-randomized experimental trial.AnimalsTwelve healthy adult sika deer (nine males and three females).MethodsDeer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg−1 or 1 mg kg−1. Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM).ResultsA two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour−1), metabolic clearance (34.6 L hour−1), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour−1), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour−1, 121.0 L hour −1, 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration.Conclusions and Clinical relevanceFollowing intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer. 相似文献
6.
槲皮素药代动力学与生物活性的研究进展 总被引:1,自引:0,他引:1
槲皮素(quercetin,QCT)是一种主要存在于水果、蔬菜、草本植物中的黄酮类化合物,近年来广受关注。本研究就2007—2016年QCT的文献分布情况进行了初步分析,发现发文量总体呈递增趋势;并对其药代动力学以及抗癌、抗肥胖、抗阿尔茨海默病、抗抑郁和免疫调节等生物活性的研究进展进行了综述,以期为QCT的深入研究和进一步开发利用提供参考。 相似文献
7.
8.
【目的】研究伊维菌素(IVM)在吉富罗非鱼体内的药物动力学,为其在罗非鱼养殖中的合理应用提供依据。【方法】将吉富罗非鱼按1mg/kg的给药剂量肌肉注射IVM,采用高效液相色谱法于给药后不同时间点对各组织进行采样检测,通过DAS 3.0药物代谢动力学软件分析IVM在吉富罗非鱼体内的药代动力学参数。【结果】在肌肉注射给药方式下,吉富罗非鱼血液中IVM质量浓度C随时间t的药物动力学模型符合一级吸收二室开放模型,其药物动力学方程为:C血液=0.215e-0.016(t-0.22)+0.198e0-0.413e-1.294(t-0.22)。肌肉注射给药后,IVM在血液及肌肉、肾脏、精巢和肝脏的峰含量(Cmax)分别为0.424mg/L及0.757,0.618,0.571,1.514mg/kg;达峰时间(Tmax)分别为8,24,8,16和24h;AUC(0-∞)分别为506.134,89.445,143.794,99.824和507.977mg/(L·h);MRT(0-∞)分别为1 810.979,176.789,194.868,312.487和259.84h;t1/2z分别为1 208.304,155.129,67.049,231.330和165.918h;各组织的药物代谢动力学方程分别为:C肌肉=4.219e-0.037t+0.217e-0.004t-4.436e-0.049t;C肾脏=0.001e-0.005t+0.713e-0.004t-0.714e-0.031t;C精巢=3.479e-0.096t+0.25e-0.003t-3.729e-0.119t;C肝脏=1.764(e-0.004t-e-0.132t)。【结论】IVM在吉富罗非鱼体内的药物动力学特征表现为:吸收快、分布广、消除缓慢。因此初步确定在水温(26±1)℃下肌肉注射1mg/kg IVM,其休药期为25d。 相似文献
9.
【目的】建立小鼠肺部感染多杀性巴氏杆菌Pasteurella multocida模型,研究马波沙星在健康小鼠和肺部感染的小鼠体内的药动学,通过分析比较两者的药动学参数,优化临床给药。【方法】采用气管插管法对小鼠进行肺部感染,对感染小鼠和健康小鼠按体质量单剂量皮下注射2 mg·kg-1的马波沙星,用高效液相色谱法测定血浆中马波沙星的浓度。用Win Nonlin5.2.1软件提供的非房室模型处理血浆药物浓度-时间数据。【结果】马波沙星在感染小鼠体内得到的药时曲线下面积(AUC)为4.58μg·m L-1·h、峰质量浓度(Cmax)为0.97μg·m L-1、平均滞留时间(MRT)为5.62 h,均显著高于(P0.05)在健康小鼠体内得到的AUC(1.67μg·m L1·h)、Cmax(0.68μg·m L-1)、MRT(2.63 h),而表观分布容积(V/F)3.12 L·kg-1和体清除率(Cl/F)0.42 L·kg-1·h-1均显著低于(P0.05)健康小鼠体内的V/F(8.61 L·kg-1)和Cl/F(1.07 L·kg-1·h-1)。【结论】多杀性巴氏杆菌感染显著增加了马波沙星的AUC、Cmax、MRT,并降低了V/F、Cl/F,而其他药动学参数无显著性差异。 相似文献
10.
在水温(25±2)℃条件下,以15 mg/kg鱼体重的剂量给奥尼罗非鱼单次口灌盐酸土霉素,采用高效液相色谱法测定血浆和肌肉组织中的药物浓度,研究盐酸土霉素在奥尼罗非鱼体内的代谢及消除规律。结果显示:血药时间数据符合一级吸收二室开放模型,半衰期(T1/2Ka、T1/2α、T1/2β)分别为4.79、4.10、45.20 h,最大血药浓度为1.50μg/m L,达峰时间为7.30 h,药时曲线下面积(AUC)为42.35μg·h/m L。肌肉作为可食性组织,选取肌肉组织作为残留检测的靶组织,以0.1 mg/kg为最高残留限量,在本试验条件下,建议休药期不低于10 d。 相似文献