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61.
Propranolol and verapamil inhibit mRNA expression of RyR2 and SERCA in L-thyroxin-induced rat ventricular hypertrophy 总被引:3,自引:1,他引:2
INTRODUCTION An important mechanism contributing to the highmortality and sudden death in patients with cardiac hy-pertrophy is ventricular arrhythmias[1]. The most con-sistently observed abnormalities are: 1) prolongation ofthe action potential duration and refractoriness; 2) non-uniform prolongation of the action potential; 3) the im-paired ability to handle intracellular calcium due tochanges in ryanodine receptor (RyR) and sarco-endo-plasmic reticulum Ca2 -ATPase (SERCA)[2,3]. Rya… 相似文献
62.
Adrian M Laurant P Berthelot A 《Clinical and experimental pharmacology & physiology》2004,31(5-6):306-313
The purpose of the present study was to determine the effects of magnesium (Mg) on the mechanical properties of resistance arteries in adult and old rats. Studies were performed in adult (17 weeks) and old (104 weeks) male Wistar rats. The vasodilatory response and the passive mechanical properties of the wall of isolated perfused and pressurized arterial segments of mesenteric small arteries were investigated after Mg and verapamil application, both known for their calcium antagonistic properties. Mesenteric resistance arteries from old rats exhibited an outward hypertrophic remodelling, with enlargment of the lumen, thickening of the media and enlarged media cross-sectional area. The vasodilatory response induced by the application of increasing extracellular concentrations of Mg and verapamil was significantly smaller in preconstricted mesenteric arteries of old rats than in those of adult rats. Incremental distensibility in response to increasing intravascular pressures did not change. However, the stress-strain curve was shifted to the left in pressurized mesenteric arteries from old rats, indicating arterial wall stiffness. Verapamil (3 micro mol/L) did not modify the stress-strain curves in either adult or aged rats. However, Mg (4.8 mmol/L) significantly shifted the curve to the right in mesenteric arteries from adult rats and, to a greater degree, in those from old rats. Although Mg-induced vasodilatation is impaired in aged rats, increased Mg concentration improved the mechanics of pressurized mesenteric resistance arteries. The fact that Mg decreases arterial stiffness in arteries from old rats suggests that Mg has a beneficial effect on age-related changes to the vascular wall. 相似文献
63.
Purpose. This study assessed the influence of mdr1a P-glycoprotein (P-gp) gene disruption, gender and concentration on initial brain uptake clearance (Cl
up) of morphine, quinidine and verapamil.
Methods. Cl
up of radiolabeled substrates was determined in P-gp-competent and deficient [mdr1a(–/–)] mice by in situ brain perfusion. Brain:plasma distribution of substrates after i.v. administration was determined in both strains.
Results. Genetic disruption of mdr1a P-gp resulted in 1.3-, 6.6- and 14-fold increases in Cl
up for morphine, verapamil and quinidine, respectively. With the exception of small differences for verapamil, gender did not affect Cl
up. Saturable transport of verapamil and quinidine was observed only in P-gp-competent mice, with apparent IC
50 values for efflux of 8.6 ± 2.3 M and 36 ± 2 M, respectively. VerapamilCl
up was 50% higher in mdr1a(+/–) vs.
mdr1a(+/+) mice; no such difference was observed for quinidine. In P-gp-competent mice, uptake of verapamil and quinidine was unaffected by organic vehicles. Plasma decreased VER Cl
up to a greater extent in the presence of P-gp. The influence of P-gp in situ was lower than, but correlated with, the effect in vivo.
Conclusions. P-gp decreases Cl
up of morphine, verapamil and quinidine in situ with little or no influence of gender, but this effect cannot fully account for the effects of P-gp in vivo. P-gp is the only saturable transport mechanism for verapamil and quinidine at the murine blood-brain barrier. The influence of protein binding on Cl
up may be enhanced by P-gp-mediated efflux. 相似文献
64.
It has been suggested that salicylate hydroxylation can be used to detect hydroxyl radical formation in vivo. In the present study we investigated the effects of verapamil and or ryanodine on salicylate (SA) and its hydroxylated adduct; 2,3-dihydroxybenzoic acid (2,3-DHBA) levels in glutamate induced neurotoxicity of whole rat brains. To detect SA and 2,3-DHBA, an HPLC-EC/UV method was used. Retention time was found to be 3.9 min for 2,3-DHBA and 12.0 min for SA. Verapamil at 10(-5) and 10(-7) and ryanodine at 10(-5) M concentrations were found to have a significant decreasing effect on this degradation induced by glutamate. This was the highest dose for ryanodine tested. As an L-type voltage dependent calcium channel blocker, verapamil was found ineffective at 10(-4), 10(-6) and 10(-8) M concentrations. Surprisingly, none of the combined application groups (verapamil + ryanodine) was found effective on SA hydroxylation. As a result, ryanodine was effective only at the highest dose, while verapamil exerts its effect in a dose dependent fashion as reported before in the literature. 相似文献
65.
目的:研究小檗胺(Ber)对ATP诱导的细胞内钙动员的作用。方法:以Fura 3-AM负载培养的VSMC和心肌细胞,共聚焦技术检测细胞内钙荧光强度的变化。结果:(1)ATP使VSMC和心肌细胞内钙升高,但VSMC核区不明显。(2)Ber对静息荧光强度无影响,但降低ATP升高的胞内钙(P<0.01),Ber 100μmol·L~(-1)延长达峰值的时间(P<0.01),并不能完全抑制ATP升高的胞内钙。(3)在无外钙时,Ber对ATP诱导的胞内钙升高无抑制作用(P>0.05)。(4)Ber的作用与维拉帕米(Ver)相似。结论:ATP引起细胞外钙内流和内钙释放,Ber可阻断ATP引起的外钙内流,对其内钙释放无影响。 相似文献
66.
Simon W. Rabkin 《Clinical and experimental pharmacology & physiology》1991,18(6):431-438
1. To evaluate and compare the effects of the calcium channel blockers, diltiazem and verapamil, on CNS modulation of blood pressure, unanaesthetized and unrestrained rats with catheters previously inserted into the lateral cerebral ventricle and femoral artery received intracerebroventricular (i.c.v.) administration of diltiazem or verapamil, 10 or 50 micrograms/kg, or their diluent. 2. Diltiazem, at both 10 and 50 micrograms/kg i.c.v., produced significant (P less than 0.05) decreases in systolic and diastolic blood pressure and heart rate. Verapamil, at 50 micrograms/kg but not at 10 micrograms/kg i.c.v., produced a significant (P less than 0.05) decrease in blood pressure, while both doses significantly (P less than 0.05) decreased heart rate. 3. To examine the endogenous opioid systems as potential modulators of the effects of these calcium antagonists, the mu opioid antagonist naloxone, 20 micrograms/kg, was administered i.c.v. either before or after each calcium antagonist. Naloxone reversed and prevented the reduction in blood pressure produced by both agents. The decrease in heart rate produced by verapamil but not diltiazem was reversed by naloxone. 4. The results suggest that: (1) calcium channels in neuron membranes in the CNS play a role in blood pressure regulation; (2) at least part of the blood pressure reduction produced by calcium blockers may be effected in the CNS; and (3) central opioid mechanisms modulate part of the action of the calcium antagonists verapamil and diltiazem on blood pressure. 相似文献
67.
对维拉帕米(VR)治疗室上性快速型心律失常(SVT)时红细胞钠泵和Na~+、K~+、Mg~(2+)变化进行对比研究,正常人30名红细胞内Na~+、K~+、Mg~(2+)分别为77.9±2.1、172.5±3.8、16.4±0.4μmol/g Hb,红细胞膜钠泵为43.9±6.1 μmol Pi/g Hb/h。SVT 33例发病时,红细胞内Na~+、K~+、Mg~(2+)为83.7±5.0、143.2±12.5、12.6±0.5 μmol/g Hb,红细胞膜钠泵为65.1±5.2μmol Pi/g Hb/h。给VR后,红细胞内Na~+明显高于正常人(P<0.05),红细胞内K~+和Mg~(2+)则低于正常人(P<0.01),红细胞膜钠泵活力仍高于正常人水平。 相似文献
68.
油茶皂甙对大鼠离体子宫平滑肌的作用 总被引:1,自引:0,他引:1
用64只离体大鼠子宫平滑肌(USM),探讨油茶皂甙(SQS)对USM作用。结果:(1)当加入SQS溶液5~10μg/ml时,对缩宫素(Oxy)及高K+去极化后所引起的USM收缩均有明显的抑制作用,但可被增加浴液中的Ca2+浓度所对抗;(2)累积量-效曲线表明,SQS与CaCl2呈非竞争性拮抗;(3)SQS尚对Oxy所致USM的依细胞内Ca2+以及依细胞外Ca2+的收缩反应均有抑制作用。结果表明SQS有抗Ca2+作用,从而能抑制USM的收缩。这在基础理论和临床实践上均有较大的意义。 相似文献
69.
Interaction of verapamil with d-tubocurarine and cholinergic agonists at the avian neuromuscular junction 总被引:1,自引:0,他引:1
F. A. Wali 《Acta anaesthesiologica Scandinavica》1987,31(1):15-20
The effect of verapamil on neuromuscular transmission and muscle contraction was studied in the skeletal muscle of chick in vitro. The interactions of verapamil with d-tubocurarine (d-TC)-induced neuromuscular blockade, acetylcholine (ACh) and tetraethylammonium (TEA)-induced contractures were also studied. The purpose of the present investigation was to see if verapamil: intensified the neuromuscular blockade produced by d-TC; modified the cholinergic responses to ACh, TEA; and inhibited both directly and indirectly elicited twitch contractions. The results showed that verapamil (1-100 micrograms/ml, 2-200 mumol/l) had a neuromuscular blocking activity on its own; i.e. it reduced both directly and indirectly evoked twitch contractions, and intensified the neuromuscular blockade produced by d-TC. In addition, verapamil reduced the contractures produced by ACh and TEA in the chick muscle. The results are in favour of the possibility that verapamil acts by a mixture of pre- and post-junctional effects at the chick neuromuscular junction. 相似文献
70.
本文用随机双盲组间对照的方法,对53例原发性高血压进行治疗对比.地尔硫组27例(男20例,女7例;年龄50±SD7yr;病程14±7yr),用最大剂量270mg/d,4wk为一疗程。维拉帕米组26例(男25例,女1例;年龄52±6yr病程14±8yr)用最大剂量360mg/d,4wk为一疗程。总有效率前者大于后者(85%,46%)但差异不显著,降压幅度亦是前者大(2.0/2.0kPa,1.0/1.0kPa,P<0.01,0.05)2药均有升高HDL-ch的作用,副作用均较轻. 相似文献