全文获取类型
收费全文 | 1851篇 |
免费 | 191篇 |
国内免费 | 106篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 27篇 |
妇产科学 | 33篇 |
基础医学 | 319篇 |
口腔科学 | 27篇 |
临床医学 | 92篇 |
内科学 | 343篇 |
皮肤病学 | 30篇 |
神经病学 | 113篇 |
特种医学 | 16篇 |
外国民族医学 | 1篇 |
外科学 | 104篇 |
综合类 | 163篇 |
现状与发展 | 1篇 |
预防医学 | 49篇 |
眼科学 | 18篇 |
药学 | 363篇 |
中国医学 | 11篇 |
肿瘤学 | 432篇 |
出版年
2024年 | 4篇 |
2023年 | 29篇 |
2022年 | 65篇 |
2021年 | 90篇 |
2020年 | 80篇 |
2019年 | 61篇 |
2018年 | 63篇 |
2017年 | 74篇 |
2016年 | 89篇 |
2015年 | 122篇 |
2014年 | 178篇 |
2013年 | 216篇 |
2012年 | 156篇 |
2011年 | 186篇 |
2010年 | 144篇 |
2009年 | 127篇 |
2008年 | 117篇 |
2007年 | 95篇 |
2006年 | 70篇 |
2005年 | 48篇 |
2004年 | 47篇 |
2003年 | 23篇 |
2002年 | 16篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有2148条查询结果,搜索用时 234 毫秒
21.
22.
23.
《Clinical nutrition (Edinburgh, Scotland)》2021,40(5):3263-3278
- Download : Download high-res image (170KB)
- Download : Download full-size image
24.
Histone deacetylase (HDAC) inhibitors, which represent a structurally diverse group of molecules, have emerged as a novel therapeutic class of molecules with significant anticancer potential. Vorinostat and romidepsin, known as the first generation of HDAC inhibitors, were approved in the United States for the treatment of T-cell lymphomas. Preliminary activity of HDAC inhibitors has also been observed in non-small cell lung cancer (NSCLC) in combination with the existing treatment regimens, of which is the focus of the current review. 相似文献
25.
Inga Hoffmann Martin Roatsch Martin L. Schmitt Luca Carlino Martin Pippel Wolfgang Sippl Manfred Jung 《Molecular oncology》2012,6(6):683-703
Reversible histone methylation has emerged in the last few years as an important mechanism of epigenetic regulation. Histone methyltransferases and demethylases have been identified as contributing factors in the development of several diseases, especially cancer. Therefore, they have been postulated to be new drug targets with high therapeutic potential. Here, we review histone demethylases with a special focus on their potential role in oncology drug discovery. We present an overview over the different classes of enzymes, their biochemistry, selected data on their role in physiology and already available inhibitors. 相似文献
26.
27.
Staphylococcal enterotoxin B (SEB) is a potent exotoxin produced by the Staphylococcus aureus. This toxin is classified as a superantigen because of its ability to directly bind with MHC-II class molecules followed by activation of a large proportion of T cells bearing specific Vβ-T cell receptors. Commonly associated with classic food poisoning, SEB has also been shown to induce toxic shock syndrome, and is also considered to be a potential biological warfare agent because it is easily aerosolized. In the present study, we assessed the ability of indole-3-carbinol (I3C) and one of its byproducts, 3,3′-diindolylmethane (DIM), found in cruciferous vegetables, to counteract the effects of SEB-induced activation of T cells in mice. Both I3C and DIM were found to decrease the activation, proliferation, and cytokine production by SEB-activated Vβ8 + T cells in vitro and in vivo. Interestingly, inhibitors of histone deacetylase class I (HDAC-I), but not class II (HDAC-II), showed significant decrease in SEB-induced T cell activation and cytokine production, thereby suggesting that epigenetic modulation plays a critical role in the regulation of SEB-induced inflammation. In addition, I3C and DIM caused a decrease in HDAC-I but not HDAC-II in SEB-activated T cells, thereby suggesting that I3C and DIM may inhibit SEB-mediated T cell activation by acting as HDAC-I inhibitors. These studies not only suggest for the first time that plant-derived indoles are potent suppressors of SEB-induced T cell activation and cytokine storm but also that they may mediate these effects by acting as HDAC inhibitors. 相似文献
28.
Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer. High EZH2 expression correlated with poor prognosis and overall survival independent of MYCN amplification status. Unexpectedly, treatment of 3 EZH2-high expressing neuroblastoma cell lines (IMR32, CHP134 and NMB), with EZH2-specific inhibitors (GSK126 and EPZ6438) resulted in only a slight G1 arrest, despite maximum histone methyltransferase activity inhibition. Furthermore, colony formation in cell lines treated with the inhibitors was reduced only at concentrations much higher than necessary for complete inhibition of EZH2 histone methyltransferase activity. Knockdown of the complete protein with three independent shRNAs resulted in a strong apoptotic response and decreased cyclin D1 levels. This apoptotic response could be rescued by overexpressing EZH2ΔSET, a truncated form of wild-type EZH2 lacking the SET transactivation domain necessary for histone methyltransferase activity. Our findings suggest that high EZH2 expression, at least in neuroblastoma, has a survival function independent of its methyltransferase activity. This important finding highlights the need for studies on EZH2 beyond its methyltransferase function and the requirement for compounds that will target EZH2 as a complete protein. 相似文献
29.
《Drug discovery today》2022,27(1):246-256
Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs. 相似文献
30.