全文获取类型
收费全文 | 664篇 |
免费 | 47篇 |
国内免费 | 32篇 |
专业分类
儿科学 | 19篇 |
基础医学 | 12篇 |
口腔科学 | 5篇 |
临床医学 | 51篇 |
内科学 | 16篇 |
皮肤病学 | 32篇 |
神经病学 | 194篇 |
特种医学 | 3篇 |
外科学 | 17篇 |
综合类 | 55篇 |
预防医学 | 5篇 |
眼科学 | 2篇 |
药学 | 300篇 |
中国医学 | 31篇 |
肿瘤学 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 7篇 |
2021年 | 9篇 |
2020年 | 14篇 |
2019年 | 11篇 |
2018年 | 18篇 |
2017年 | 12篇 |
2016年 | 11篇 |
2015年 | 19篇 |
2014年 | 24篇 |
2013年 | 38篇 |
2012年 | 36篇 |
2011年 | 27篇 |
2010年 | 28篇 |
2009年 | 21篇 |
2008年 | 31篇 |
2007年 | 24篇 |
2006年 | 22篇 |
2005年 | 20篇 |
2004年 | 24篇 |
2003年 | 35篇 |
2002年 | 26篇 |
2001年 | 23篇 |
2000年 | 14篇 |
1999年 | 7篇 |
1998年 | 22篇 |
1997年 | 16篇 |
1996年 | 13篇 |
1995年 | 19篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 10篇 |
1991年 | 18篇 |
1990年 | 13篇 |
1989年 | 15篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 12篇 |
1985年 | 12篇 |
1984年 | 13篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1977年 | 3篇 |
1976年 | 7篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有743条查询结果,搜索用时 15 毫秒
101.
Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics 下载免费PDF全文
Grimm SW Richtand NM Winter HR Stams KR Reele SB 《British journal of clinical pharmacology》2006,61(1):58-69
AIMS: To explore the potential for drug interactions on quetiapine pharmacokinetics using in vitro and in vivo assessments. METHODS: The CYP enzymes responsible for quetiapine metabolite formation were assessed using recombinant expressed CYPs and CYP-selective inhibitors. P-glycoprotein (Pgp) transport was tested in MDCK cells expressing the human MDR1 gene. The effects of CYP3A4 inhibition were evaluated clinically in 12 healthy volunteers that received 25 mg quetiapine before and after 4 days of treatment with ketoconazole 200 mg daily. To assess CYP3A4 induction in vivo, 18 patients with psychiatric disorders were titrated to steady-state quetiapine levels (300 mg twice daily), then titrated to 600 mg daily carbamazepine for 2 weeks. RESULTS: CYP3A4 was found to be responsible for formation of quetiapine sulfoxide and N- and O-desalkylquetiapine and not a Pgp substrate. In the clinical studies, ketoconazole increased mean quetiapine plasma C(max) by 3.35-fold, from 45 to 150 ng ml(-1) (mean C(max) ratio 90% CI 2.51, 4.47) and decreased its clearance (Cl/F) by 84%, from 138 to 22 l h(-1) (mean ratio 90% CI 0.13, 0.20). Carbamazepine decreased quetiapine plasma C(max) by 80%, from 1042 to 205 ng ml(-1) (mean C(max) ratio 90% CI 0.14, 0.28) and increased its clearance 7.5-fold, from 65 to 483 l h(-1) (mean ratio 90% CI 6.04, 9.28). CONCLUSIONS: Cytochrome P450 3A4 is a primary enzyme responsible for the metabolic clearance of quetiapine. Quetiapine pharmacokinetics were affected by concomitant administration of ketoconazole and carbamazepine, and therefore other drugs and ingested natural products that strongly modulate the activity or expression of CYP3A4 would be predicted to change exposure to quetiapine. 相似文献
102.
AIM: To assess the effects of anti-epileptic drugs on renal tubular function. METHODS: Urinary N-acetyl-beta-D-glucosaminidase activity was measured in 114 epileptic children (mean age 5.6 +/- 1.1 years) who were undergoing monotherapy with valproate (n = 46), carbamazepine (n = 34), lamotrigine (n = 13) and combined therapy with valproate+carbamazepine (n = 21). RESULTS: The urinary N-acetyl-beta-D-glucosaminidase index of valproate (P < 0.01), carbamazepine (P < 0.05) and polytherapy group (P < 0.01) were significantly elevated when compared with that of the control group. No significant difference in N-acetyl-beta-D-glucosaminidase levels was found between the lamotrigine group and the control subjects. We found that the distribution of the N-acetyl-beta-D-glucosaminidase values of patients depended significantly on the length of therapy (P < 0.01). The level of urinary excretion of N-acetyl-beta-D-glucosaminidase was significantly higher in the patients who were taking long-term treatment (>10 years) with valproate, carbamazepine and combined therapy than those taking therapy shorter than 10 years (P < 0.01). The mean serum concentrations of valproate and carbamazepine were 68.7 +/- 17.44 microg/mL and 5.41 +/- 1.23 microg/mL, respectively. There was a significant correlation between the serum concentration of valproate and urinary N-acetyl-beta-D-glucosaminidase levels (r = 0.44, P < 0.01). There was also a significant correlation between the serum concentration of carbamazepine and N-acetyl-beta-D-glucosaminidase excretion (r = 0.52, P < 0.01). CONCLUSION: The present study demonstrated that in patients treated with valproate and carbamazepine, an impairment of tubular function can be present, whereas lamotrigine does not cause any significant change. 相似文献
103.
Comparison of the effects of benzodiazepines and other anticonvulsant drugs on synthesis and utilization of 5-HT in mouse brain 总被引:1,自引:0,他引:1
Acute administration of clonazepam (0.5-8.0 mg/kg, i.p.), diazepam (2-32 mg/kg, i.p.), chlordiazepoxide (1-40 mg/kg, i.p.) or diphenylhydantoin (5-320 mg/kg, i.p.), caused a dose-related elevation of the concentrations of, 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan in whole mouse brain. Carbamazepine (5-100 mg/kg, i.p.), and phenobarbitone (10-80 mg/kg, i.p.) raised the concentrations of 5-HT and 5-HIAA in the brain, whereas flurazepam (5-80 mg/kg, i.p.) only elevated the level of 5-HIAA. After administration of L[G-3H]tryptophan (25 microCi, s.c.), clonazepam (4 mg/kg), diazepam (32 mg/kg, i.p.), chlordiazepoxide (40 mg/kg) or diphenylhydantoin (40 mg/kg), but not carbamazepine (50 mg/kg), flurazepam (40 mg/kg) or phenobarbitone (80 mg/kg), increased the content of labelled tryptophan in brain. However, administration of drugs did not alter the incorporation of the label into [3H]5-HT, suggesting that the synthesis of 5-HT was unaffected. When incorporation of [3H]tryptophan into [3H]5-HT was complete and the pool of labelled 5-HT was decreasing, clonazepam, diazepam, chlordiazepoxide and diphenylhydantoin elevated the content of [3H]5-HT in brain. Flurazepam, phenobarbitone and carbamazepine were without apparent effect. Calculation of the rate of utilization of 5-HT (Km) showed that all drugs, apart from flurazepam, reduced the utilization of 5-HT. Using the rate of disappearance of 5-HT after inhibition of tryptophan hydroxylase by p-chlorophenylalanine (PCPA), all drugs, except flurazepam, diphenylhydantoin and phenobarbitone, decreased the utilization of 5-HT. The major action of the anticonvulsant drugs on the function of 5-HT in brain appears to be a decrease in the utilization of 5-HT without altering synthesis. 相似文献
104.
ABSTRACT. A case of carbamazepine-induced intermittent total atrioventricular block with asystole and Stokes-Adams attacks is reported. The diagnosis was proved by repeated administration of carbam-azepine after insertion of a demand pacemaker. If syncopes occur or change nature in a patient treated with carbamazepine, evaluation of cardiac conduction is recommended. 相似文献
105.
Mark Swerdlow MD MSc FFARCS Consultant J.G. Cundill MB ChB BSc Registrar 《Anaesthesia》1981,36(12):1129-1132
The value of anticonvulsant drugs in the treatment of some cases of lancinating pain is now established. The results in 170 consecutive cases in an ongoing series are reported with special reference to the efficacy of four anticonvulsants--carbamazepine, clonazepam, phenytoin and valproate. The findings are discussed. 相似文献
106.
R. Kamiński B. Przywara M. Gasior Z. Kleinrok S. J. Czuczwar 《Journal of neural transmission (Vienna, Austria : 1996)》1998,105(2-3):133-146
Summary. 5-Fluoroindole-2-carboxylic acid, an antagonist of the glycine site within the NMDA receptor complex, administered intraperitoneally
in doses of 150 and 200 mg/kg, 120 min before electroconvulsions, significantly raised the convulsive threshold from 6.8 to
7.9 and 8.3 mA, respectively. At lower doses, it did not influence the threshold. However, lethality was observed 24h after
administration of the threshold-elevating doses of this glycine site antagonist.
5-Fluoroindole-2-carboxylic acid (100 mg/kg), applied together with carbamazepine, valproate or phenobarbital, significantly
reduced their ED50 values against maximal electroshock – from 13.9 to 7.5 mg/kg, from 291 to 242 mg/kg, and from 18.6 to 11.1 mg/kg, respectively.
At the dose of 50 mg/kg, it also potentiated the protective activity of carbamazepine. However, 5-fluoroindole-2-carboxylic
acid, up to 100 mg/kg, did not affect the anticonvulsive activity of diphenylhydantoin.
When applied at doses equal to their ED50 values against maximal electroshock-induced convulsions, carbamazepine (13.9 mg/kg), phenobarbital (18.6 mg/kg) and valproate
(291 mg/kg) did not affect the motor performance of mice in the chimney test. 5-Fluoroindole-2-carboxylic acid (100 mg/kg)
produced a significant motor impairment, at 50 mg/kg it did not affect the motor performance. The combined treatment of 5-fluoroindole-2-carboxylic
acid (100 mg/kg) with carbamazepine, phenobarbital or valproate, providing a 50% protection against maximal electroshock,
resulted in motor impairment. Only the combination of 5-fluoroindole-2-carboxylic acid (50 mg/kg) with carbamazepine (8.6
mg/kg) did not significantly influence this parameter.
Almost all of the antiepileptic drugs studied, when administered at doses equal to their ED50 values against maximal electroshock, did not influence retention in the passive avoidance task, which is a measure of long-term
memory. Only valproate (291 mg/kg) worsened long-term memory. The combined treatment of 5-fluoroindole-2-carboxylic acid (100
mg/kg) with carbamazepine or phenobarbital, providing a 50% protection against maximal electroshock, did not affect the retention.
The combination of 5-fluoroindole-2-carboxylic acid (100 mg/kg) with valproate (242 mg/kg) caused a significant impairment
of long-term memory and mortality of 50% of animals 24 h following the administration. The results suggest that the blockade
of the strychnine-insensitive glycine site may lead to an enhancement of the protective activity of some conventional antiepileptic
drugs, which is associated with pronounced side-effects and lethality in some cases.
Accepted January 9, 1998; received July 28, 1997 相似文献
107.
A pharmacological study of the effect of carbamazepine on neuromuscular transmission in the rat diaphragm 总被引:1,自引:0,他引:1
M C Tsai 《Neuropharmacology》1985,24(4):345-351
The effects of carbamazepine (0.042-0.42 mM) on neuromuscular transmission were studied on the isolated rat phrenic nerve diaphragm preparation using standard pharmacological and electrophysiological methods. Carbamazepine decreased (1) the antidromic activity of the phrenic nerve, (2) the amplitude of the endplate potential (EPP) and miniature endplate potential (MEPP), (3) the quantal content of the endplate potential, (4) the indirectly-elicited twitch tension, (5) the muscle contracture in chronically denervated muscle induced by acetylcholine (ACh) and (6) the amplitude of the compound phrenic nerve action potential, in a concentration-dependent manner. The antidromic activity of the phrenic nerve was the most affected, while the phrenic nerve compound action potential was least affected. However, the IC50 for carbamazepine (the concentration of carbamazepine that inhibited 50% of the response) was in the same order of concentration, i.e. 0.11-0.3 mM. Compared with the effect of carbamazepine on the indirectly-elicited twitch tension with its actions described above, it is concluded that carbamazepine interfered with the neuromuscular activity by inhibiting pre- and postsynaptic process and conduction in the phrenic nerve. 相似文献
108.
目的:探讨服用卡马西平对成人癫痫患者骨密度的影响,分析骨密度变化的相关因素。方法:对32例单一服用卡马西平6个月以上的成年癫痫患者及30名健康成人的骨密度进行检测及比较,同时测定癫痫患者血钙浓度、血磷浓度、药物浓度及总碱性磷酸酶。结果:服用卡马西平组腰1~腰4各椎体平均骨密度Z值较正常对照组明显减低(P=0.002)。患者腰椎部骨密度Z值与体质量呈正相关(B=0.06,P=0.012),女性赋值为-1,结果骨密度Z值与性别关系为B=-0.67,P=0.006。结论:服用卡马西平可引起成人癫痫患者骨密度减低,绝经前女性受影响较男性小,体质量是保护性因素。 相似文献
109.
110.
Ying-hui Chen Cui-cui Wang Xia Xiao Li Wei Guoxiong Xu 《Acta pharmacologica Sinica》2013,34(4):473-479