全文获取类型
收费全文 | 902982篇 |
免费 | 63748篇 |
国内免费 | 2338篇 |
专业分类
耳鼻咽喉 | 12538篇 |
儿科学 | 28798篇 |
妇产科学 | 26241篇 |
基础医学 | 127361篇 |
口腔科学 | 24758篇 |
临床医学 | 75165篇 |
内科学 | 184003篇 |
皮肤病学 | 19153篇 |
神经病学 | 71889篇 |
特种医学 | 36618篇 |
外国民族医学 | 338篇 |
外科学 | 142675篇 |
综合类 | 19089篇 |
一般理论 | 247篇 |
预防医学 | 64796篇 |
眼科学 | 20125篇 |
药学 | 64203篇 |
中国医学 | 1806篇 |
肿瘤学 | 49265篇 |
出版年
2018年 | 9106篇 |
2017年 | 7209篇 |
2016年 | 7747篇 |
2015年 | 8826篇 |
2014年 | 12467篇 |
2013年 | 19351篇 |
2012年 | 25850篇 |
2011年 | 27463篇 |
2010年 | 16690篇 |
2009年 | 15901篇 |
2008年 | 26315篇 |
2007年 | 27928篇 |
2006年 | 28109篇 |
2005年 | 27605篇 |
2004年 | 26431篇 |
2003年 | 25629篇 |
2002年 | 25207篇 |
2001年 | 41489篇 |
2000年 | 42728篇 |
1999年 | 36405篇 |
1998年 | 10026篇 |
1997年 | 9199篇 |
1996年 | 9114篇 |
1995年 | 8473篇 |
1994年 | 8103篇 |
1993年 | 7621篇 |
1992年 | 28260篇 |
1991年 | 27043篇 |
1990年 | 26476篇 |
1989年 | 25410篇 |
1988年 | 23621篇 |
1987年 | 23224篇 |
1986年 | 22314篇 |
1985年 | 21212篇 |
1984年 | 15862篇 |
1983年 | 13530篇 |
1982年 | 8115篇 |
1979年 | 14638篇 |
1978年 | 10259篇 |
1977年 | 8660篇 |
1976年 | 8173篇 |
1975年 | 8993篇 |
1974年 | 10735篇 |
1973年 | 10224篇 |
1972年 | 9703篇 |
1971年 | 8960篇 |
1970年 | 8627篇 |
1969年 | 8062篇 |
1968年 | 7720篇 |
1967年 | 7131篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
51.
52.
Weiyu Ye Anna Olsson-Brown Robert A. Watson Vincent T. F. Cheung Robert D. Morgan Isar Nassiri Rosalin Cooper Chelsea A. Taylor Umair Akbani Oliver Brain Rubeta N. Matin Nicholas Coupe Mark R. Middleton Mark Coles Joseph J. Sacco Miranda J. Payne Benjamin P. Fairfax 《British journal of cancer》2021,124(10):1661
Background Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10−6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma 相似文献
53.
54.
55.
56.
57.
58.
N. S. Hari Narayana Moorthy Sergio F. Sousa Maria J. Ramos Pedro A. Fernandes 《Medicinal chemistry research》2016,25(7):1340-1357
Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets. 相似文献
59.
60.
F. Giovanardi F. Nudo Q. Lai M. Garofalo A. Consolo E. Choppin De Janvry G.A. Arroyo Murillo P. Ursi D. Stabile F. Melandro P.B. Berloco R. Pretagostini L. Poli 《Transplantation proceedings》2019,51(1):128-131