首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   148篇
  免费   8篇
  国内免费   1篇
耳鼻咽喉   1篇
妇产科学   3篇
基础医学   4篇
临床医学   7篇
内科学   14篇
神经病学   2篇
外科学   2篇
综合类   9篇
预防医学   5篇
药学   105篇
中国医学   4篇
肿瘤学   1篇
  2023年   1篇
  2021年   1篇
  2019年   1篇
  2016年   1篇
  2015年   1篇
  2014年   1篇
  2013年   4篇
  2012年   1篇
  2011年   1篇
  2010年   2篇
  2008年   3篇
  2007年   2篇
  2006年   2篇
  2005年   2篇
  2004年   1篇
  2003年   4篇
  2002年   1篇
  2001年   3篇
  2000年   1篇
  1999年   5篇
  1998年   5篇
  1997年   5篇
  1996年   3篇
  1995年   3篇
  1994年   8篇
  1993年   3篇
  1992年   4篇
  1991年   7篇
  1990年   11篇
  1989年   7篇
  1988年   5篇
  1987年   10篇
  1986年   4篇
  1985年   4篇
  1984年   5篇
  1983年   2篇
  1982年   6篇
  1981年   3篇
  1980年   5篇
  1979年   4篇
  1978年   4篇
  1977年   6篇
  1976年   1篇
  1975年   1篇
  1974年   1篇
  1973年   2篇
排序方式: 共有157条查询结果,搜索用时 15 毫秒
1.
1‐Aminobenzotriazole (ABT) is a well‐known in vivo nonspecific inhibitor of cytochrome P450 (CYP) enzymes. An effective dosing regimen of ABT for a multiple‐administration study is needed to conduct pharmacological studies for proof‐of‐concept, although it has been established for single‐administration study, to characterize the pharmacokinetics of drug candidates. This study demonstrated a suitable dosing vehicle of ABT for continuous administration and increased exposure to antipyrine, which is a nonspecific probe of CYP, using ABT for a long period in mice. The dosing vehicle of ABT was 0.5% (w/v) hydroxypropyl methylcellulose and 0.5% (v/v) Tween 80 in N,N‐dimethylacetamide/20% hydroxypropyl‐β‐cyclodextrin aqueous solution (2:8, v/v) based on the duration of apparent solubility. After implantation of an ALZET osmotic pump with ABT, the plasma concentrations of ABT were maintained at more than 4.1 μg/ml over 336 h. Compared with the vehicle group, the CLtot of antipyrine with ABT decreased to approximately one‐fourth, and the BA of antipyrine with ABT increased up to 3‐fold. In addition, the enhancement of exposure of antipyrine by ABT was maintained over the 336 h. The body weight, food consumption and hematological parameters of mice did not change with ABT administration for 16 days. These findings demonstrated that pretreatment of ABT can increase long‐term exposure using continuous administration with the ALZET osmotic pump in mice with no overt toxicity. It is concluded that the in vivo use of 1‐aminobenzotriazole can be applied to pharmacological studies for proof‐of‐concept, thus contributing to the selection of drug candidates at an early drug discovery stage. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   
2.
目的建立HPLC法测定复方柳安咖注射液中水杨酸钠、安替比林和咖啡因的含量。方法色谱柱:Agela TechnologiesC18柱(150mm×4.6mm,5μm);流动相:0.02mol.L-1磷酸二氢钠溶液(用磷酸调节pH 2.6)-乙腈-甲醇(70∶15∶15);检测波长:280nm;柱温:35℃;流速:1.0mL.min-1;进样量:20μL。结果水杨酸钠、安替比林和咖啡因线性范围分别为13.79~124.1(r=0.999 9),4.016~36.14(r=0.999 9)和2.078~18.70μg.mL-1(r=0.999 9);平均回收率分别为100.1%(RSD为0.5%),100.0%(RSD为0.5%)和100.5%(RSD为0.4%)。结论该方法灵敏、准确、快速,专属性强,可有效地控制复方柳安咖注射液中水杨酸钠、安替比林、咖啡因的含量。  相似文献   
3.
The effect of deltamethrin pretreatment on the pharmacokinetics and metabolism of antipyrine was studied in male rats. The total plasma clearance of antipyrine was significantly decreased by deltamethrin pretreatment (20 mg/kg and 40 mg/kg daily for 6 days prior to antipyrine administration), while the elimination half-life at phase, the area under the concentration-time curve and the mean residence time of antipyrine were significantly increased. The magnitude of the observed changes was dose dependent. The urinary excretion of norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine was decreased by 39%, 32% and 26%, respectively (p<0.001) in the presence of deltamethrin. In addition, the rate constants for formation of each of these metabolites were significantly decreased by an average of approximately 71%. These results suggest that deltamethrin is capable of inhibiting oxidative metabolism, a finding which could be of clinical and toxicological significance.  相似文献   
4.
Summary The effects over 1 year of an oestrogendominant oral contraceptive containing ethinylestradiol and levonorgestrel on serum high-density lipoprotein cholesterol, apolipoproteins A-I and A-II and liver microsomal enzyme activity assessed by antipyrine kinetics, were investigated in 21 healthy, young women. HDL cholesterol and apolipoprotein concentrations rose and hepatic microsomal enzyme activity fell during the first month of the treatment, and remained affected throughout the year. After discontinuation of treatment, the lipid and apolipoprotein concentrations and the microsomal enzyme activity returned to their pretreatment levels within 1 month. The drug, by reducing hepatic enzyme activity, may have influenced both the antipyrine elimination rate and the high-density lipoprotein concentration.  相似文献   
5.
Summary We have compared the effects of two dietary regimens with different macronutrient compositions — a macrobiotic diet and a Western diet — on drug metabolism and plasma lipids in seven healthy volunteers.The macrobiotic diet, high in carbohydrate, low in protein and fat, and devoid of animal food sources, was eaten for a ten day control period, as was the Western diet, high in calories, fat, and protein, as well as animal food sources. We determined the influences of these diets on the clearance of orally administered antipyrine, oxazepam, and methadone, as well as on plasma lipids.There was a statistically significant change in antipyrine clearance as well as in plasma LDL-cholesterol and HDL-cholesterol after the dietary periods. This suggests that the influence of dietary changes may have some effect on the clearance of therapeutic drugs. However, this is not universal and is probably important when the drug is highly dependent on the mixed-function oxidase system.  相似文献   
6.
Summary The relationship between acetylator phenotype and the inhibitory effect of cimetidine on the hepatic metabolism of antipyrine has been studied in 20 subjects. Cimetidine, 1,0 g/day resulted in a significant decrease in the metabolic clearance rate of antipyrine, but only in slow acetylators, as fast acetylators were less affected. No sex difference was observed. No major change occurred in the urinary excretion of D-glucaric acid, which means that cimetidine had not-affected that Phase II reaction. It did significantly decrease the urinary partial clearance rate of norantipyrine, leaving that of antipyrine and 4-OH-antipyrine unchanged, which suggests that cimetidine had preferentially inhibited the P 450 isozyme that catalyses norantipyrine formation.  相似文献   
7.
Antipyrine (AP) is a commonly used probe of oxidative metabolism. Indirect evidence demonstrates formation rate limited disposition of its metabolites. Kinetic studies using antipyrine and its major metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), and 4-hydroxyantipyrine (OHA) were completed to investigate the metabolic fate of preformed antipyrine metabolite and to demonstrate directly formation rate-limited metabolite disposition in vivo. Bolus injections of antipyrine and preformed metabolites (40-50 mg/kg) were administered to male, New Zealand white rabbits. Plasma and urine were analyzed using HPLC. These studies demonstrate that HMA, NORA, and OHA are formation rate limited in the rabbit. NORA appears to undergo further extensive oxidative and conjugative metabolism. Unknown additional peaks were detected in urine after NORA dosing but not after HMA or OHA administration. Mass spectroscopy of the unknown HPLC eluents identified potential structures of these NORA metabolites.  相似文献   
8.
The unit impulse response theory has been adapted to characterize the transport profile of drugs into the central nervous system (CNS). From the obtained input function, the cumulative plasma volume (V) cleared by transport into the CNS in time can be calculated. Simulation studies demonstrated that transport governed by passive diffusion resulted in a linear relationship between V and time, while the slope of the line, the blood- brain barrier (BBB) clearance, proved to be an adequate and model independent parameter to characterize drug transport into the CNS. The error in the result of the numerical procedure could be limited to less than 10% of the theoretically predicted value. Superposition of 5 or 10% random noise on simulated data did not result in significant differences between the calculated and theoretically predicted clearance values. Simulations of carrier-mediated transport resulted in nonlinear transport curves; the degree of nonlinearity, and thus the detectability, was dependent on the initial degree of saturation of the system, the rate of desaturation, as caused by drug elimination processes and the noise level on the data. In vivoexperiments in the rat were performed, using atenolol, acetaminophen, and antipyrine as model drugs. Linear transport relationships were obtained for all drugs, indicating that transport was dependent on passive diffusion or a low affinity carrier system. BBB- clearance values were 7±1 l/min for atenolol, 63±7 ul/min for acetaminiphen and 316±25 l/min for antipyrine. These experiments validate the applicability of the presented technique in in vivostudies.  相似文献   
9.
目的:对安痛定注射液中的三组分实行分光光度法同时测定。方法:对传统的多波长线性回归分光光度法进行改进,使其不需要等吸收波长。结果:9份模拟样品中氨基比林、安替比林、巴比妥的平均回收率分别为99.9%、99.8%、100.3%,相对标准偏差分别为0.5%、1.0%、1.7%。对3个批号实际样品的测定结果与标准方法一致。结论:方法简便快捷,适于安痛定注射液的制剂分析。  相似文献   
10.
 目的:研究钙离子拮抗剂地尔硫(DZ)对模型药安替比林(AP)在人体内代谢的选择性抑制作用。方法:6名健康男性志愿者,随机分成二组,分别po单剂量AP 800mg及加服DZ(30mg,tid),6d,取血并留尿48h,间隔2周后交叉给药。HPLC法测定血浆AP浓度和尿液中AP、3-羟甲基安替比林(3-OHMAP)、4-羟基安替比林(4-OHAP)、N-去甲基安替比林(NorAP)的浓度。结果:加服DZ后,APt1/2(Ke)从(13.79±3.17)h延长至(18.54±3.14)h(P<0.01),Cls从(40.42±7.62)ml·min-1减少至(28.64±5.84)ml·min-1(P<0.01),cmaxAUC明显增加(P<0.05)。4-OHAP尿清除率从(12.91±3.40)ml·min-1减少至(3.50±0.78)ml·min-1(P<0.01),3-OHMAP和NorAP的尿清除率没有明显变化。结论:DZ选择性地抑制了AP在人体肝脏中的4-羟基化代谢途径,提示DZ是一作用较强的、选择性的肝药酶抑制剂。  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号