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Michael M Gezalian Luigi Mangiacotti Padmesh Rajput Nicklaus Sparrow Konrad Schlick Shouri Lahiri 《Journal of cerebral blood flow and metabolism》2021,41(4):693
Adrenoceptor and calcium channel modulating medications are widely used in clinical practice for acute neurological and systemic conditions. It is generally assumed that the cerebrovascular effects of these drugs mirror that of their systemic effects – and this is reflected in how these medications are currently used in clinical practice. However, recent research suggests that there are distinct cerebrovascular-specific effects of these medications that are related to the unique characteristics of the cerebrovascular anatomy including the regional heterogeneity in density and distribution of adrenoceptor subtypes and calcium channels along the cerebrovasculature. In this review, we critically evaluate existing basic science and clinical research to discuss known and putative interactions between adrenoceptor and calcium channel modulating pharmacotherapies, the neurovascular unit, and cerebrovascular anatomy. In doing so, we provide a rationale for selecting vasoactive medications based on lesion location and lay a foundation for future investigations that will define neuroprotective paradigms of adrenoceptor and calcium channel modulating therapies to improve neurological outcomes in acute neurological and systemic disorders. 相似文献
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Ineffectiveness of organic calcium channel blockers in antagonizing long-term potentiation 总被引:1,自引:0,他引:1
Evidence has accumulated suggesting that the presence of calcium is critical for development of hippocampal long-term potentiation (LTP). However, there is a paucity of information about whether calcium's role in LTP is pre- or postsynaptic. In the present study, we examined the effectiveness of nitrendipine, verapamil, flunarizine and the benzodiazepine diazepam in: blocking voltage-dependent calcium channels; blocking synaptic transmission; and preventing development of LTP. Using the in vitro slice preparation, we obtained intracellular and extracellular recordings from guinea pig hippocampal CA1 pyramidal cells. At the cellular level, all 4 drugs were ineffective in blocking voltage-dependent calcium spikes (TTX resistant) and the calcium-dependent afterhyperpolarization. Verapamil and diazepam appeared to antagonize synaptic transmission, as reflected in smaller population spike amplitudes. Development of long-term potentiation was not affected by the presence of verapamil, flunarizine and diazepam. Nitrendipine appeared to reduce the percentage of slices exhibiting LTP; however, ethanol, the vehicle used to dissolve nitrendipine, was shown in separate experiments to reduce the percentage of slices exhibiting LTP. These results suggest that neither the organic calcium channel blockers--nitrendipine, verapamil, and flunarizine--nor micromolar concentrations of diazepam are potent blockers of extrasynaptic voltage-sensitive calcium channels in hippocampus. They thus cannot be used to demonstrate a specific pre- or postsynaptic calcium role in LTP. 相似文献
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体外短波热疗联合前列腺灸及哈乐治疗非细菌性前列腺炎和前列腺痛疗效观察 总被引:5,自引:1,他引:4
目的 探讨慢性非细菌性前列腺炎(CNP)和前列腺痛(PD)的治疗方法。方法 应用体外短波热疗联合前列腺灸及α1A-肾上腺素能受体阻滞剂哈乐治疗CNP和PD患者26例,疗程8周。观察治疗前后前列腺炎症状评分(CPSI)与最大尿流率(MFR)变化。结果 有效率为80.8%。治疗前后CPSI和MFR均有显著改善(P〈0.05)。结论 体外短波热疗联合前列腺灸及哈乐治疗CNP和PD安全有效。 相似文献
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静脉预注H1,H2受体阻滞药对减轻鱼精蛋白副作用的研究 总被引:3,自引:0,他引:3
将30例ASD、VSD患者随机分为对照与预防用药两组,对比观察H1、H2受体阻滞药苯海拉明、西米替丁对减轻鱼精蛋白副作用的效果和应用鱼精蛋白后补体C3、C4、CH50浓度变化。结果发现预防用药组血液动力学变化明显小于对照组,两组之间差异显著(P<0.01)。应用鱼精蛋白后C3、C4、CH50均下降,与用药前相比差异显著(P<0.01)。提示鱼精蛋白中和肝素可引起补体激活、组胺释放,H1、H2受体阻滞药能够减轻鱼精蛋白引起的血压下降。 相似文献
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采用细胞内微电极记录技术,同步观察了3,6-[二甲氨基]-二苯并碘因甲酸盐(IHC-64)对豚鼠心乳头肌细胞动作电位和收缩力的作用。50μmol/L IHC-64抑制心肌收缩力,而不影响快反应动作电位。增加IHC-64浓度,动作电位0相最大峰值(APA)、除极速率(dp/dt_(max))和复极50%和90%时程(APD_(50)、APD_(90))被明显抑制。IHC-64抑制慢反应动作电位,提高细胞外钙浓度可拮抗这种抑制。结果提示,IHC-64主要抑制慢Ca~(2+)内流,同时也部分抑制快Na~+内流,它可能是一种新型B类钙通道阻滞剂。 相似文献
9.
目的:观察血管紧张素受体拮抗剂(ARBs)L158,809和血管紧张素转换酶(ACE)抑制剂西拉普利对体外培养人肾小球系膜细胞转化生成因子(TGF—β1)表达和纤维连接蛋白、层粘连蛋白和Ⅳ型胶原分泌的影响。方法:分别在不同葡萄糖浓度(5.6mmol/L和30mmol/L)和药物浓度(1、10、100和500μmol/L)下体外培养人肾小球系膜细胞,分别于24、48和72h后测定细胞增殖。然后将系膜细胞分为低糖(5.6mmol/L)对照组(LG)、高糖(30mmol/L)对照组(HG)、L158,809(10μmol/L)组和西拉普利(10μmmol/L)组,48h后,分别用RT-PCR法测定TGF-β1表达,ELISA和放射免疫法测定细胞上清液中TGF-β1、纤维连接蛋白、层粘连蛋白和Ⅳ胶原浓度。结果:与低糖对照组相比,高糖对照组系膜细胞过度增殖,细胞上清液中TGF-βl、纤维连接蛋白、层粘连蛋白和Ⅳ胶原浓度明显升高,TGF-βlmRNA表达也显升高;而L158,809组和西拉普利组TGF-β1和细胞外基质(ECM)蛋白水平明显低于高糖对照组,且TGF-β1mRNA水平亦表达明显降低。结论:高糖可刺激体外培养系膜细胞过度增殖,TGF-β1表达增高,ECM蛋白分泌明显增加,而L158,809和西拉普利均可抑制高糖环境下上述现象。 相似文献
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S. Lindgren S. Larsson M. Holgerssonr B. Bake 《Clinical physiology and functional imaging》1994,14(2):169-179
Summary. To investigate the ability of various lung-function tests to demonstrate dilatation of peripheral airways, ten asthmatics inhaled increasing doses of a f2-agonist by two different and controlled techniques. Low inspiratory flow with a long post-inspi-ratory pause favoured peripheral deposition, and a high inspiratory flow with a short post-inspiratory pause favoured central deposition of drug in the airways. Ordinary spirometry, maximum expiratory flow rates after breathing air as well as a helium-oxygen mixture, a single breath N2-test and resistance of the respiratory system were obtained before and after each of five terbutaline doses with both inhalation techniques. By using a double-dummy technique, the study could be performed double blinded. Effects were compared at doses giving equal effects on PEF, assumed to represent equal deposition of bronchodilator and effects on central airways. At such ‘iso A PEF doses’, particularly FVC and the slope of phase III of the N2-test improved more following the slow inhalation technique. It is concluded that changes in those tests reflect dilatation in peripheral airways in asthmatics., 相似文献