全文获取类型
收费全文 | 6581篇 |
免费 | 575篇 |
国内免费 | 12篇 |
专业分类
7168篇 |
出版年
2024年 | 9篇 |
2023年 | 68篇 |
2022年 | 131篇 |
2021年 | 224篇 |
2020年 | 110篇 |
2019年 | 169篇 |
2018年 | 189篇 |
2017年 | 183篇 |
2016年 | 238篇 |
2015年 | 348篇 |
2014年 | 336篇 |
2013年 | 438篇 |
2012年 | 531篇 |
2011年 | 492篇 |
2010年 | 315篇 |
2009年 | 239篇 |
2008年 | 329篇 |
2007年 | 335篇 |
2006年 | 289篇 |
2005年 | 285篇 |
2004年 | 218篇 |
2003年 | 192篇 |
2002年 | 224篇 |
2001年 | 147篇 |
2000年 | 192篇 |
1999年 | 131篇 |
1998年 | 50篇 |
1997年 | 29篇 |
1996年 | 33篇 |
1995年 | 46篇 |
1994年 | 34篇 |
1993年 | 32篇 |
1992年 | 69篇 |
1991年 | 58篇 |
1990年 | 59篇 |
1989年 | 58篇 |
1988年 | 44篇 |
1987年 | 33篇 |
1986年 | 42篇 |
1985年 | 48篇 |
1984年 | 26篇 |
1983年 | 23篇 |
1982年 | 13篇 |
1981年 | 16篇 |
1980年 | 10篇 |
1979年 | 19篇 |
1978年 | 12篇 |
1977年 | 15篇 |
1976年 | 10篇 |
1972年 | 6篇 |
排序方式: 共有7168条查询结果,搜索用时 31 毫秒
991.
Shizukuda Y Matoba S Mian OY Nguyen T Hwang PM 《Molecular and cellular biochemistry》2005,273(1-2):25-32
Use of the chemotherapeutic agent doxorubicin (Dox) is limited by dose-dependent cardiotoxic effects. The molecular mechanism underlying these toxicities are incompletely understood, but previous results have demonstrated that Dox induces p53 expression. Because p53 is an important regulator of the cell birth and death we hypothesized that targeted disruption of the p53 gene would attenuate Dox-induced cardiotoxicity. To test this, female 6–8 wk old C57BL wild-type (WT) or p53 knockout (p53 KO) mice were randomized to either saline or Dox 20 mg/kg via intraperitoneal injection. Animals were serially imaged with high-frequency (14 MHz) two-dimensional echocardiography. Measurements of left ventricle (LV) systolic function as assessed by fractional shortening (FS) demonstrated a decline in WT mice as early as 4 days after Dox injection and by 2 wk demonstrated a reduction of 31± 16% (P < 0.05) from the baseline. In contrast, in p53 KO mice, LV FS was unchanged over the 2 wk period following Dox injection. Apoptosis of cardiac myocytes as measured by the TUNEL and ligase reactions were significantly increased at 24 h after Dox treatment in WT mice but not in p53 KO mice. After Dox injection, levels of myocardial glutathione and Cu/Zn superoxide dismutase were preserved in p53 KO mice, but not in WT animals. These observations suggest that p53 mediated signals are likely to play a significant role in Dox-induced cardiac toxicity and that they may modulate Dox-induced oxidative stress.These two authors equally contributed to this study. 相似文献
992.
993.
Burns MR Wood SJ Miller KA Nguyen T Cromer JR David SA 《Bioorganic & medicinal chemistry》2005,13(7):2523-2536
Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a focused library of lysine-spermine conjugates with lipopolysaccharide (LPS) have been characterized. Lysine-spermine conjugates with the epsilon-amino terminus of the lysinyl moiety derivatized with long-chain aliphatic hydrophobic substituents in acyl or alkyl linkage bind and neutralize bacterial lipopolysaccharides, and may be of use in the prevention or treatment of endotoxic shock states. 相似文献
994.
995.
996.
997.
998.
Thyroid nodules (TN) are a common clinical problem. Fine needle aspiration (FNA) of the thyroid now is practiced worldwide and proves to be the most economical and reliable diagnostic procedure to identify TNs that need surgical excision and TNs that can be managed conservatively. The key for the success of thyroid FNA consists of an adequate or representative cell sample and the expertise in thyroid cytology. The FNA cytologic manifestations of TNs may be classified into seven working cytodiagnostic groups consisting of a few heterogenous lesions each to facilitate the differential diagnosis. Recent application of diagnostic molecular techniques to aspirated thyroid cells proved to be useful in separating benign from malignant TNs in several cases of indeterminate lesions. 相似文献
999.
Scaffolding proteins exist in eukaryotes to properly assemble signaling proteins into specific multimeric functional complexes. JLP is a novel leucine zipper protein belonging to a family of scaffolding proteins that assemble JNK signaling modules. JLP is a proline-rich protein that contains two leucine zipper domains and a highly conserved C-terminal domain. We have identified kinesin light chain 1 (KLC1) as a binding partner for the second leucine zipper domain of JLP using yeast two-hybrid screening. The interaction domain of KLC1 was mapped to its tetratripeptide repeat, which contains a novel leucine zipper-like domain that is crucial for the interaction with JLP. Mutations of Leu-280, Leu-287, Val-294, and Leu-301 within this domain of KLC1 disrupted its ability to associate with JLP. Immunofluorescence studies showed that JLP and KLC1 co-localized in the cytoplasm and that the localization of JLP was dependent on its second leucine zipper. Ectopic expression of a dominant negative form of KLC1 resulted in the mislocalization of endogenous JLP. Moreover, the association between JLP and KLC1 occurred in vivo and was important in the formation of ternary complex with JNK1. These results identify a novel protein-protein interaction between KLC1 and JLP that involves leucine zipper-like domains and support the role of motor proteins in the spatial regulation of signaling modules. 相似文献
1000.