全文获取类型
收费全文 | 397篇 |
免费 | 8篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 1篇 |
妇产科学 | 1篇 |
基础医学 | 23篇 |
临床医学 | 25篇 |
内科学 | 102篇 |
皮肤病学 | 3篇 |
神经病学 | 9篇 |
特种医学 | 6篇 |
外科学 | 32篇 |
综合类 | 51篇 |
预防医学 | 9篇 |
药学 | 144篇 |
2篇 | |
中国医学 | 2篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 8篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 2篇 |
2017年 | 7篇 |
2016年 | 2篇 |
2015年 | 6篇 |
2014年 | 7篇 |
2013年 | 22篇 |
2012年 | 22篇 |
2011年 | 18篇 |
2010年 | 14篇 |
2009年 | 14篇 |
2008年 | 8篇 |
2007年 | 23篇 |
2006年 | 15篇 |
2005年 | 20篇 |
2004年 | 18篇 |
2003年 | 13篇 |
2002年 | 16篇 |
2001年 | 12篇 |
2000年 | 9篇 |
1999年 | 6篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 8篇 |
1995年 | 10篇 |
1994年 | 14篇 |
1993年 | 6篇 |
1992年 | 5篇 |
1991年 | 10篇 |
1990年 | 15篇 |
1989年 | 9篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 8篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有410条查询结果,搜索用时 15 毫秒
91.
P. E. Hicks C. Tierney S. Z. Langer 《Naunyn-Schmiedeberg's archives of pharmacology》1985,328(4):388-395
Summary Vasoconstrictor responses mediated by the 2-adrenoceptor agonist TL99, were particularly sensitive to blockade by the calcium antagonist drug diltiazem in isolated perfused tail arteries of spontaneously hypertensive rats (SHR). In contrast, the vasoconstrictor responses induced by the 1-adrenoceptor agonist methoxamine were significantly more resistant to antagonism by diltiazem. At higher concentrations (>300 nmol/l) diltiazem became an effective antagonist of all -adrenoceptor mediated responses. In normotensive Wistar Kyoto (WKY) or Sprague-Dawley (SD) rats diltiazem was significantly less potent againts vasoconstrictor responses to TL99 than in SHR. The blockade of 1-adrenoceptor mediated vasoconstriction by diltiazem was not significantly different when normotensive rats and SHR were compared. The vasoconstrictor responses evoked by 5HT in the perfused tail arteries were particularly resistant to blockade by diltiazem in SHR arteries.The responses to endogenously released noradrenaline, evoked by electrical field stimulation, were significantly antagonised by diltiazem (30 nmol/l–3 mol/l) in SHR-tail arteries, while they were not modified in WKY-tail arteries. At the concentrations of diltiazem which blocked end organ responses to field stimulation, there was no modification of total tritium overflow SHR-tail arteries after labelling the tissue with3H-noradrenaline, indicating that diltiazem does not inhibit transmitter release at these concentrations.The tail artery preparation of SHR contains a population of postsynaptic 2-adrenoceptors which mediate contraction in this blood vessel and the calcium entry blocker diltiazem is a potent antagonist of vasoconstrictor responses mediated by vascular 2-adrenoceptors in hypertensive rats. These findings may be relevant to the antihypertensive action of diltiazem. 相似文献
92.
目的:探讨硫氮卓酮对慢性低O2高CO2大鼠肺动脉压力的影响及其作用机制。方法:将Sprague-Dawley大鼠分为正常对照组(A组)、四周低O2高CO2组(B组)和四周低O2高CO2+硫氮卓酮组(C组),采用透射电镜、图像分析、免疫组化、原位杂交等方法,研究硫氮卓酮对慢性低O2高CO2大鼠肺动脉平均压(mPAP)、颈动脉平均压(mCAP)及肺动脉显微和超微结构、肺动脉结构型一氧化氮合酶(ceNOS)及其基因表达的影响。结果:①B组mPAP明显高于A组(P<0.01),C组mPAP明显低于B组(P<0.01),A组和B组mCAP无明显差异(P>0.05),C组mCAP低于B组(P<0.01);②光镜下,肺细小动脉管壁面积/管总面积比值(WA/TA)C组明显低于B组(P<0.01);电镜下,C组大鼠肺细小动脉内皮损伤、中膜平滑肌细胞和胶原纤维增生明显轻于B组;③免疫组化见C组肺细小动脉ceNOS的平均吸光度值明显高于B组(P<0.01);原位杂交发现C组肺细小动脉ceNOS mRNA平均吸光度值明显高于B组(P<0.01)。结论:硫氮卓酮可抑制慢性低O2高CO2性肺动脉高压形成和肺血管结构重建,肺动脉ceNOS及其基因表达的增加为其重要作用机制,硫氮卓酮可能为治疗COPD、肺动脉高压伴高血压或室上性心律失常患者较为理想的药物。 相似文献
93.
S. H. Kim Kyung Woo Cho S. H. Chang Sung Zoo Kim Soo Wan Chae 《Pflügers Archiv : European journal of physiology》1997,434(4):362-372
The mechanism by which glibenclamide regulates mechanically activated atrial natriuretic peptide (ANP) secretion was investigated
using isolated perfused rat atria. A reduction in atrial pressure from an experimentally imposed distending pressure stimulated
the secretion of ANP and caused concomitant translocation of extracellular fluid (ECF) into the atrial lumen. The activation
of ANP secretion and ECF translocation were closely correlated with atrial volume changes and the increase in ANP secretion
was a function of the ECF translocation. Glibenclamide (1, 10, 100 μM), an ATP-sensitive K+ (K+
ATP) channel blocker, had no effect on the basal secretion of ANP, suppressed the stimulation of stretch-activated ANP secretion
in a dose-dependent manner, but not the translocation of the ECF. Glipizide (100 μM) and tolbutamide (100 μM), other K+
ATP channel blockers, had similar effects to those of glibenclamide. Suppression by glibenclamide (100 μM) of the stretch-induced
ANP secretion was not observed in atria that had been pretreated with pinacidil (200 μM), an ATP-sensitive K+ channel opener: pinacidil alone had no effect on ECF translocation and ANP secretion. Furthermore, blocking Ca2+ influx by using the Ca2+ channel blocker diltiazem (10 nM), or a Ca2+-depleted medium prevented the suppression of stretch-induced ANP secretion by glibenclamide. In other experiments, atrial
distension produced a slight membrane depolarization of cardiomyocytes; this was accentuated in the presence of glibenclamide.
Furthermore, in single cardiomyocytes, glibenclamide increased the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. From these results, we suggest that glibenclamide suppresses atrial release of ANP by blocking
K+
ATP channels and increasing Ca2+ influx and that the K+
ATP channels are associated with the regulation of the mechanically activated ANP secretion from the atria.
Received: 13 May 1996 / Received after revision: 10 February 1997 / Accepted: 5 March 1997 相似文献
94.
The aim of this study evaluated the spinal anesthetic effect of verapamil and diltiazem. After rats were injected intrathecally with verapamil and diltiazem, dose–response curves were constructed. We evaluated the potency and duration of verapamil or diltiazem which compared with mepivacaine, a commonly used local anesthetic, in rats. Verapamil, diltiazem and mepivacaine produced a dose-dependent local anesthetic effect as spinal anesthesia. On a 50% effective dose (ED50) basis, the spinal anesthetic effect of verapamil was more potent than diltiazem or mepivacaine (P < 0.01 for each comparison). On an equipotent basis (ED25, ED50, and ED75), the blockade duration of spinal anesthesia caused by diltiazem was longer than that caused by verapamil or mepivacaine (P < 0.01 for each comparison). In summary, verapamil produced more potent spinal blockades, when compared with diltiazem or mepivacaine. Diltiazem demonstrated longer spinal blockades than did verapamil or mepivacaine. 相似文献
95.
96.
The purpose of this study was to investigate the effects of resveratrol, an antioxidant, on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. The pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined after an oral administration of diltiazem (15 mg/kg) to rats in the presence and absence of resveratrol (0.5, 2.5, and 10 mg/kg). Compared to the control group, the presence of resveratrol significantly (P < 0.05) increased the area under the plasma concentration–time curve (AUC) of diltiazem, except for resveratrol 0.5 mg/kg. Consequently, the absolute bioavailability (AB) of diltiazem in the presence of resveratrol (2.5 and 10 mg/kg) was significantly (P < 0.05) higher (10.2–11.1%) than that of the control (6.9%). The relative bioavailability (RB) of diltiazem in the presence of resveratrol (2.5 and 10 mg/kg) was increased by 1.48‐ to 1.60‐fold. Resveratrol did not alter absorption rate constant (Ka) and the time to reach the peak concentration (Tmax) of diltiazem. The AUC of desacetyldiltiazem was increased significantly (P < 0.05) in the presence of 10 mg/kg of resveratrol. The metabolite–parent AUC ratio (MR) in the presence of resveratrol was decreased but did not show significant change. In conclusion, resveratrol significantly increased the bioavailability of diltiazem due to the inhibition of both the cytochrome P450 (CYP) 3A4‐mediated metabolism and the efflux pump P‐glycoprotein (P‐gp) in the intestine and/or liver. Based on these results, if these results would be confirmed in clinical experiments, the dosage of diltiazem should be readjusted when diltiazem is used concomitantly with resveratrol. 相似文献
97.
目的 观察静脉滴注地尔硫治疗难治性心绞痛的临床疗效及安全性。方法10例难治性心绞痛患者停用静脉点滴硝酸甘油及口服β-受体阻滞剂后,静点地尔硫40~150μg/min(2.4~9 mg/h)持续48 h。结果与用药前48小时相比,7例患者心绞痛发作显著改善,其中5例完全控制,2例明显改善。3例(30%)无效,经联合应用静脉硝酸甘油后1例完全控制,2例明显改善。无严重低血压、缓慢心律失常及心功能恶化等不良反应发生;无急性心肌梗死、需要急诊介入治疗及死亡发生。8例患者在病情稳定后1周内行介入检查与治疗,其中5例接受PTCA及支架置入术,3例接受冠状动脉旁路移植术。结论静脉滴注地尔硫40~150μg/min(2.4~9 mg/h)或者联合应用静脉硝酸甘油为难治性心绞痛提供了一种较为安全有效的药物治疗手段,值得临床进一步深入探讨。 相似文献
98.
Slices of guinea-pig olfactory cortex have been used to compare the potency of various Ca-blockers on the electrophysiology of synaptic transmission. Listed in the order of potency, the divalent cations Cd2+, Ni2+, Mn2+, Co2+, La3+ and Mg2+ depressed synaptic transmission. The organic Ca-blockers, nifedipine or nimodipine or verapamil and diltiazem were ineffective up to 0.01 nmol/l. Verapamil, D600 or diltiazem (0.1–0.3 mmol/l) depressed both synaptic transmission and the sodium-mediated presynaptic action potential. These results reaffirm the idea that “organic Ca-antagonist’ do not block all Ca-channels in brain and the high Cd2+ sensitivity suggests the Ca-channels in post- and presynaptic membranes have dissimilar pharmacological profiles. 相似文献
99.
Erling N. Petersen 《European journal of pharmacology》1986,130(3):323-326
The dihydropyridine Bay K 8644 exerts a positive modulation of Ca2+ channels. Administration of Bay K 8644 3–5 mg/kg i.p. to rats induces within 15 min a severe spasticity syndrome consisting of stiff tail, arched back, stretching and twisting of forelimbs and hindlegs and backwards motility and rolling over. The syndrome was effectively antagonized by nifedipine 3–30 mg/kg but not by the other Ca2+ channel blockers flunarizine, diltiazem and verapamil. Diltiazem even enhanced the spasticity. Diazepam 10–30 mg/kg i.p. completely blocked the spasticity whereas the other muscle relaxants (−)-baclofen and the β-carboline ZK 93423 were completely inactive. These findings with Bay K 8644 suggest that spasticity may be caused by changed Ca2+ homeostasis. 相似文献
100.
地尔硫卓对猪急性心肌梗死再灌注后无再流的影响 总被引:2,自引:3,他引:2
Zhao JL Yang YJ You SJ Jing ZC Wu YJ Yang WX Meng L Tian Y Chen JL Gao RL Chen ZJ 《中华医学杂志》2005,85(10):679-683
目的评价地尔硫卓防治猪急性心肌梗死(AMI)再灌注后无再流的作用。方法实验动物随机分成对照组、地尔硫卓组(2mg/min冠脉内)和假手术组。前两组行冠状动脉结扎3h,松解1h制备AMI再灌注模型。AMI前、后和再灌注后均行血流动力学测定和心肌声学造影(MCE)检查,最终行病理学分析。结果与AMI前相比,对照组AMI后3h、左室收缩压(LVSP)、心排量(CO)和左心室内压最大收缩和舒张变化速率(±dp/dtmax)均显著下降(均P<0.05,P<0.01),左室舒张末压(LVEDP)显著升高(P<0.01);再灌注后1h仅LVSP显著恢复(P<0.05),然而±dp/dtmax继续显著下降(P<0.05);而地尔硫卓组AMI后3h各项指标变化与对照组相同;但再灌注后1h LVEDP、±dp/dtmax和CO均显著恢复(均P<0.05),且比对照组更显著(均P<0.05)。对照组MCE和病理染色所测的冠脉结扎区心肌范围(LA)高度一致(P>0.05),再灌注后无再流范围(ANR)分别为78.5%和82.3%,心肌坏死范围(NA)占LA的98.5%;而地尔硫卓组两方法所测LA均与对照组相当(均P>0.05),但ANR仅分别为20.6%和19.9%,NA又与对照组差异无统计学意义(P>0.05)。对照组再灌注即刻和再灌注后1h冠脉血流量仅占AMI前的45.8%和50.6%(均P<0.01),而地尔硫卓组冠脉血流量分别提高到80.4%和79.3%,比对照组增加均有统计学意义(均P<0.01)。结论 相似文献