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41.
Calcium release from intracellular stores plays an important role in the regulation of muscle contraction and electrical signals that determine the heart rhythm. The ryanodine receptor (RyR) is the major calcium (Ca^2+) release channel required for excitation-contraction coupling in the heart. Recent studies have demonstrated that RyR are macromolecular complexes comprising of 4 pore-forming channel subunits, each of which is associated with regulatory subunits. Clinical and experimental studies over the past 5 years have provided compelling evidence that intracellular Ca^2+ release channels play a pivotal role in the development of cardiac arrhythmias and heart failure. Changes in the channel regulation and subunit composition are believed to cause diastolic calcium leakage from the sarcoplasmic reticulum, which could trigger arrhythmias and weaken cardiac contractility. Therefore, cardiac RyR have emerged as potential therapeutic targets for the treatment of heart disease. Consequently, there is a strong desire to identify and/or develop novel pharmacological agents that may target these Ca^2+ signaling pathways. Pharmacological agents known to modulate RyR in the heart, and their potential application towards the treatment of heart disease are discussed in this review. 相似文献
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目的:考察5种注射剂盐酸林可霉素注射液,盐酸精氨酸注射液,注射用玻璃酸酶,肝素钠注射液和顺铂注射液的细菌内毒素检查法可行性。方法:中国药典细菌内毒素检查法。结果;除d外,其余原液及稀释液均于有干扰作用。结论:d的原液及a的20倍以上稀释液可用灵敏度为0.5EU/ml的鲎试剂作细菌内毒素检查,而b,c和e尚需进一步探讨。 相似文献
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阿克拉霉素A聚氰基丙烯酸异丁酯毫微粒冻干针剂体内外抗肝癌活性 总被引:6,自引:0,他引:6
阿克拉霉素A聚氰基丙烯酸异丁酯毫微粒的冻干针剂,能明显抑制体外培养人肝癌细胞株7703的生长,IC50为0.28μg·ml-1。在0.8μg·ml-1浓度时,克隆形成抑制率为90%,抑制作用有明显剂量依赖关系而未见明显时间依赖关系。静脉给药后,对常位移植人肝癌模型裸小鼠的抑瘤率为86.84%,肿瘤细胞增殖活性阳性率为20.83%。体内外均显示明显的抗肝癌活性,且体内抗肝癌活性比阿克拉霉素A冻干针剂强。 相似文献
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This article aims to understand the effects of rationalized health programs (the basic components of which are efficiency, calculability, predictability and control) on local practices. We discuss how a successful U.S. intervention in preventive youth health care (the Nurse Family Partnership) has been translated and adapted within a Dutch setting. The Dutch version of the program is called 'PreCare'. The empirical analysis highlights the effects of rationalized health programs on local practices, in terms of the amount of work required, how local practices are disciplined, how these programs (re)draw boundaries, the 'travel expenditures' involved (and developed 'coping strategies'), and how local practices (try to) reshape the program. Our empirical analysis builds on a combination of qualitative methods. We conducted 16 semi-structured interviews with 19 people involved in the PreCare program. The majority of the interviews were conducted between July and November 2008. We also conducted an analysis of relevant documents related to the PreCare intervention and protocol. Furthermore, we observed at several meetings, including case conferences and management intervision meetings. The article makes a theoretical and practical contribution to the field. Theoretically, we show how the rationalization process is linked to a broader development of quantification and how both developments are based on a particularly modern ontology and epistemology in which what is considered 'real' and 'knowledgeable' becomes closely tied to what is measurable. The article offers a different conceptualization of rationalized health programs, one that acknowledges the need to standardize some elements, but also recognizes the need to be open and flexible toward local practices. We specifically focus on the tools that are able to deal with both the need to standardize and the need to be open toward local practices. We suggest that '(re)writing devices' are a fruitful category of tools for this purpose. 相似文献
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Angiogenesis-independent cardioprotection in FGF-1 transgenic mice 总被引:10,自引:0,他引:10
Buehler A Martire A Strohm C Wolfram S Fernandez B Palmen M Wehrens XH Doevendans PA Franz WM Schaper W Zimmermann R 《Cardiovascular research》2002,55(4):768-777
OBJECTIVE: This study was performed to evaluate the cardioprotective role of acidic fibroblast growth factor-1 (FGF-1) in transgenic mice with cardiac-specific overexpression of human FGF-1. METHODS: Mice were subjected to coronary artery occlusion for 15-75 min with a continuously recorded 3-lead electrocardiogram (ECG). Infarct size was measured and ERK-1 and -2 activity was assessed by Western blot analysis. Creatine kinase and lactate dehydrogenase activity as marker for cell viability were measured in isolated ventricular myocytes subjected to simulated ischemia. RESULTS: Infarct development was markedly delayed in transgenics with first signs of myocardial infarction visible at 45 min after coronary artery occlusion compared to 15 min in wildtype. Maximal infarct size (60% of risk area) did not differ, but transgenics reached maximal infarction after 75 min compared to 45 min in wildtype animals. ECG revealed delayed Q-wave development and delayed ST-segment elevation in transgenics. Creatine kinase and lactate dehydrogenase release was significantly attenuated from isolated transgenic myocytes at 4 and 8 h after simulated ischemia. The delay in infarct development is partially due to a constitutive higher expression of the extracellular signal-regulated kinases ERK-1 and -2 in the myocardium of transgenics. Additionally, injection of the ERK-1/2 inhibitor UO126 decreased the cardioprotective effect of FGF-1. CONCLUSION: Cardiac specific overexpression of FGF-1 provides cardioprotection at the level of the cardiac myocyte, independent from angiogenesis, and at least partially mediated via activation of the mitogen activated protein kinase (MAP) ERK-1 and -2. 相似文献
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9-(2-膦酰甲氧乙基)腺嘌呤及其位置异构体3-(2-膦酰甲氧乙基)腺嘌呤的合成和抗病毒活性研究 总被引:1,自引:0,他引:1
Phosphonylmethoxyethyl)adenine (1),PMEA,an acyclic nucleotide withbroad-spectrum antiviral activity was synthesized with some modifications of Holy's procedure.Simutaneously,an N-3 regioisomer(2)of PMEA and a by-preduct, formaldehyde di-[2-(9-adenyl)ethyl] acetal(7)were seperated by silica gel chromatography in the ratio of 50:10:1.Compound(2)and(7) are new compounds that we have not yet found in literatures. The structure of them weredetermined with 1HNMR,2DNMR, MS and Spot test.Antiviral test showed that N-3 isomer(2)completely lost activity against both HIV-1 and HSV-1 in vitro. It seems that regiospecificity of theacyclic nucleotide structure is important for antiviral activity. 相似文献