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1.
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
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In order to establish the determination method of ivermectin (IVM) in the ivermectin microemulsion injection by high performance liquid chromatography (HPLC), Hypersil ODS2 colunm (5 μm,4.6 mm×250 mm) was used in this study. The mobile phase composed of methanol, acetonitrile and water (35:60:5,V/V/V) at a flow rate of 1 mL/min. The detection wave length was set at 244 nm and the column temperature was 30 ℃. The results showed that the HPLC system suitability of IVM was good. A good linear correlation of IVM was observed within the concentration range 80 to 320 μg/mL, and the average recovery rate was 101.90%±2.94% with RSD was 2.88%, the regression equation was Y=22 700X+2 510 (R2=0.9998). The RSD of IVM content in ivermectin microemulsion injection was 1.86%. The method was accurate and reliable,reproducible,easy to operate, which could be used in new type of ivermectin microemulsion injection. The method could be used as the basis of quality control and establishing a quality standard, and to provide basis for quality evaluation, also can provide reliable reference for safe veterinary clinical application in the future. 相似文献
4.
本文全面综述了现代兽用杀虫剂:有机磷、氨基甲酸酯、拟除虫菊酯等类药物的使用现状和近来国内外探索新的药物和给药方法。1.改变传统的喷雾和浸洗为现代泼背和点背。2.广谱驱虫药伊维菌素的问世,使得经口或皮下、肌肉注射治疗外寄生虫病的方法变为现实。3.采取持续释放装置或加入缓释剂,免去了重复用药的麻烦。 相似文献
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C. P. Daurio E. N. Cheung A. R. Jeffcoat B. J. Skelly 《Veterinary research communications》1992,16(2):125-130
The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (C
max) of ivermectin administered in the standard tablet formulation at 6 and 100 µg/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics.C
max and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 µg/kg. Furthermore,C
max was similar following administration of radiolabelled ivermectin at 6 µg/kg in either a beef-based chewable formulation or in the standard tablet formulation. 相似文献
7.
Ivermectin was injected subcutaneously into five pigs at the usual dose rate of 300 µg/kg and found to distribute well to all tissues and body fluids which were sampled 24 h post-injection. Ivermectin was detected in the contents and mucus at all levels of the gastrointestinal tract. The drug was excreted in bile, with high concentrations of the drug in the intestines and faeces. High concentrations of ivermectin were measured in skin, ears and ear wax, suggesting that the drug should be effective in the treatment of ectoparasitic infestations, particularly ear mites. The high lipid solubility of the drug may explain the high concentrations found in ear wax and skin. Ivermectin was also detected in the body fluids and tissues of an untreated pig penned with the treated animals. Direct contact appeared to be necessary for transfer of ivermectin from the treated to the untreated pig but coprophagia or urine drinking is a possible explanation.The pharmacokinetics of ivermectin administered subcutaneously at a dose rate of 300 µg/kg to six pigs were studied. There was marked individual variation in the pharmacokinetics of ivermectin. In one pig the area under the plasma concentration-time curve was particularly high. This may reflect individual variation in uptake and excretion of the drug. The mean elimination half-life of the drug was 35.2 h, suggesting that the drug is cleared slowly from pigs with drug detectable in plasma for 6–10 days. This persistence should allow a short period of protection before re-infection with parasites. 相似文献
8.
Ivermectin is one of the most commonly used drugs in pharmacotherapy of parasitic diseases in domestic and wild animals caused
by parasitic nematodes and arthropods. However, ivermectin and other avermectins very often produce side-effects in hosts.
The most dominant clinical symptom of ivermectin toxicity in domestic and wild animals is CNS depression. In nematodes, the
target site of ivermectin’s action is glutamate-gated chloride-channel receptor and GABA receptor. The depressive effect of
ivermectin in mammals might include more than one mechanism; therefore, the anticonvulsive effect of ivermectin against convulsions
caused by lidocaine and strychnine was evaluated. Ivermectin antagonized lidocaine- and strychnine-induced convulsions in
rats, although these have different mechanisms. In the present study, the anticonvulsive ED50 of ivermectin for lidocaine-induced convulsions was 2.44 mg/kg (95% CL 1.67 to 3.57 mg/kg), whereas for convulsions induced
by strychnine it was higher at 4.25 mg/kg (95% CL 2.32 to 3.78 mg/kg). At the same time, both anticonvulsive doses are significantly
lower then the observed LD50 of ivermectin (18.20 mg/kg). Furthermore, flumazenil (0.1 and 0.2 mg/kg), an antagonist of benzodiazepine receptors, antagonizes
just one part of these anticonvulsive effects of ivermectin. Our results show the significant anticonvulsive properties of
ivermectin and support the findings that ivermectin in the CNS of mammals produces multiple inhibitory effects, probably through
participation in the function of GABA-sensitive and GABA-insensitive chloride channels. 相似文献
9.
We report the results of investigations that were conducted in a sheep flock in Uttaranchal, India where repeated failure
of anthelmintic medication was noted. The study revealed that Haemonchus contortus in sheep had developed resistance to benzimidazoles (fenbendazole, mebendazole and albendazole), imidazothiazole (levamisole)
and salicylanide (rafoxanide), while it was fully susceptible to avermectins (ivermectin). Further, the suppression of nematode
egg output in faeces of sheep naturally infected with multiple anthelmintic-resistant H. contortus following treatment with ivermectin tablet (0.4 mg/kg body weight (bw), orally), ivermectin injection (1% w/v, 0.2 mg/kg
bw, subcutaneously) and ivermectin pour-on (0.5 w/v, 0.5 mg/kg bw) was also studied over a period of 10 weeks post treatment.
It was noted that ivermectin tablet after initial clearance of infection (faecal egg count reduction 100%), could not prevent
establishment of new patent natural infection for even a single day, while ivermectin pour-on and injection prevented the
establishment of new infection for 7 and 14 days post treatment, respectively. Maximum protection period (duration for which
mean faecal egg count of sheep reaches 500 eggs per gram of faeces or more) of 68 days was recorded in sheep treated with
injectable ivermectin, followed by pour-on (60 days) and oral (53 days) preparations. 相似文献
10.
Challenge with an equal mix of drug-resistant and drug-susceptible larvae of Teladorsagia circumcincta resulted in infections in groups of lambs (n = 6) either untreated or given controlled-release capsules, containing either albendazole or ivermectin. Lambs treated with albendazole capsules contained similar numbers of adult worms at necropsy to the other groups but had no detectable faecal egg count. Animals treated with ivermectin capsules had similar worm burdens and faecal egg counts to the control group but the worms had significantly higher numbers of eggs in utero. These results provide evidence for suppression of egg production by both anthelmintic treatments. The observation that albendazole caused a significant reduction in the developmental success of parasite eggs also has implications for the use of faecal egg count as an indicator for pasture contamination with resistant parasites. In two further groups of lambs, either untreated or given albendazole capsules, treatment caused a significant reduction in egg count and adult worm burden of Trichostrongylus colubriformis. No significant effects were observed on in utero egg counts or egg viability and the apparent effect on the number of eggs produced in faeces per adult female was not significant (p = 0.077). There was, therefore, no evidence that albendazole controlled-release capsules caused suppression of egg output in this species. 相似文献