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联合新型Bcl-2反义核酸与足叶乙苷抑制人小细胞肺癌细胞的增殖 总被引:1,自引:3,他引:1
目的 研究一种新型Bcl 2反义寡核苷酸 F95 1在与足叶乙苷 (VP16 )联合使用时 ,对人小细胞肺癌细胞增殖的影响。方法 分别单独及联合应用F95 1、VP16于人小细胞肺癌细胞株NCI H4 4 6 ,通过MTT法检测细胞存活率 ,通过集落形成法检测集落生存率 ,按Welander法计算联合应用组的预测值 ,通过实测值与预测值的比较进行效应分析。结果 细胞存活率 (MTT法 )和集落生存率 (集落形成法 )均显示联合应用F95 1、VP16组的实测值明显低于预测值。结论 联合应用F95 1与VP16对人小细胞肺癌细胞的增殖有协同的抑制作用。 相似文献
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目的 :观察阳离子脂质体 (DOTAP DOPE)介导的 β1肾上腺素能受体mRNA反义寡核苷酸 (β1 AS ODN)对肾性高血压大鼠血流动力学及心肌肥厚的影响。方法 :建立二肾一夹 (2K1C)肾性高血压大鼠模型 ,随机分为假手术组、模型组、反向寡核苷酸组、反义寡核苷酸组和卡维地洛 (carvedilol)组。ODN与DOTAP DOPE以 1 2摩尔比混合 ,4周末尾静脉注射 0 .5mg·kg-1,卡维地洛 10mg·kg-1·d-1灌胃 4周。定期测血压 ,8周末测血流动力学参数 ,左室重量指数 (LVWI)及血浆内皮素 1(ET 1)浓度 ,并对LVWI与ET 1进行线性相关分析。结果 :与反向寡核苷酸组比 ,β1 AS ODN能降低血压最高达39mmHg并持续 2 7d(30 .4 4± 6 .5 0 ,P <0 .0 1) ,降低左室收缩压 (LVSP) (P <0 .0 5 )、左室舒张末压 (LV EDP) (P <0 .0 1) ,升高左室最大收缩和舒张速率 (±dp dtmax) (P <0 .0 1) ,降低LVWI(P <0 .0 5 )及血浆ET 1(P <0 .0 1) ;与卡维地洛组比 ,各指标均无显著性差异。LVWI与ET 1显著正相关 (r =0 .74 9,P <0 .0 1)。结论 :DOTAP DOPE介导的 β1 AS ODN单剂量静脉注射能持续降压 ,改善血流动力学 ,预防心肌肥厚 ,可能与其降低血浆ET 1有关。 相似文献
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Sung‐Whi Rhee Radhakrishnan P. Iyer John E. Coughlin Seetharamaiyer Padmanabhan Jeremiah P. Malerich Mary J. Tanga 《Journal of labelled compounds & radiopharmaceuticals》2012,55(6):197-200
The 35S‐labeled, dinucleoside phosphorothioate 1, an orally available agent against hepatitis B virus, was prepared in eight steps with high specific activity and radiochemical purity. Radiolabeled 3H‐benzodithiole‐3‐one‐1,1‐dioxide was synthesized in four steps from 35S8 and was used as the sulfurizing reagent. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
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《Inhalation toxicology》2013,25(8):452-463
AbstractAntisense oligonucleotides (ASOs) bind and facilitate degradation of RNA and inhibit protein expression in pathways not easily targeted with small molecules or antibodies. Interleukin (IL)-4 and IL-13 potentiate signaling through the shared IL-4 receptor-α (IL-4Rα) subunit of their receptors. ASO targeting of IL-4Rα mRNA in a mouse model of asthma led to attenuation of airway hyperactivity, demonstrating potential benefit in asthma patients. This study focused on tolerability of inhaled IL-4Rα-targeting ASOs. Toxicity studies were performed with mouse- (ISIS 23189) and human-specific (ISIS 369645) sequences administered by inhalation. Four week (monkey) or 13 week (mouse) repeat doses at levels of up to 15?mg/kg/exposure (exp) and 50?mg/kg/exp, respectively, demonstrated dose-dependent effects limited to increases in macrophage size and number in lung and tracheobronchial lymph nodes. The changes were largely non-specific, reflecting adaptive responses that occur during active exposure and deposition of ASO and other material in the lung. Reversibility was observed at a rate consistent with the kinetics of tissue clearance of ASO. Systemic bioavailability was minimal, and no systemic toxicity was observed at exposure levels appreciably above pharmacological doses and doses proposed for clinical trials. 相似文献
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《Expert opinion on investigational drugs》2013,22(6):1197-1205
Although the standard approach to myeloid leukaemias remains chemotherapy, the agents currently available rarely result in cure. Recent advances in understanding the biology of these disorders have lead to the development of targeted treatment strategies. In acute promyelocytic leukaemia (APL), all-trans retinoic acid (ATRA), sodium phenylbutyrate and arsenic trioxide are agents which either induce differentiation or apoptosis and have been used to successfully achieve remission. The tyrosine kinase inhibitor, STI-571, antisense oligonucleotides, and bcr-abl vaccines are strategies which focus on the oncogenic events in chronic myelogenous leukaemia (CML). Two anti-CD33 monoclonal antibody conjugates, Y90-HuM195 and CMA-676, have been used in acute myelogenous leukaemia (AML) and have shown some efficacy. Although the preliminary results with these targeted therapies are promising, further studies are needed to establish them as effective, less toxic alternatives to the current standard of care. 相似文献
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The European pharmaceutical regulatory system has not yet been challenged by issues related to highly personalized medicines such as those to be found with active substances that affect RNA biochemistry. We review the current status of RNA-based pharmacology and present three possible case histories. The implications for the European pharmaceutical regulatory system are discussed. 相似文献
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