全文获取类型
收费全文 | 2403400篇 |
免费 | 200529篇 |
国内免费 | 4324篇 |
专业分类
耳鼻咽喉 | 34665篇 |
儿科学 | 73537篇 |
妇产科学 | 63403篇 |
基础医学 | 338780篇 |
口腔科学 | 68072篇 |
临床医学 | 219206篇 |
内科学 | 474502篇 |
皮肤病学 | 48408篇 |
神经病学 | 203730篇 |
特种医学 | 97181篇 |
外国民族医学 | 887篇 |
外科学 | 365621篇 |
综合类 | 56827篇 |
现状与发展 | 2篇 |
一般理论 | 1007篇 |
预防医学 | 193424篇 |
眼科学 | 56207篇 |
药学 | 179926篇 |
5篇 | |
中国医学 | 4420篇 |
肿瘤学 | 128443篇 |
出版年
2018年 | 25157篇 |
2017年 | 19503篇 |
2016年 | 21276篇 |
2015年 | 24122篇 |
2014年 | 34752篇 |
2013年 | 52425篇 |
2012年 | 71106篇 |
2011年 | 74870篇 |
2010年 | 43920篇 |
2009年 | 42096篇 |
2008年 | 70845篇 |
2007年 | 75453篇 |
2006年 | 76258篇 |
2005年 | 74149篇 |
2004年 | 71216篇 |
2003年 | 68932篇 |
2002年 | 67906篇 |
2001年 | 112685篇 |
2000年 | 116690篇 |
1999年 | 98569篇 |
1998年 | 28193篇 |
1997年 | 25757篇 |
1996年 | 25655篇 |
1995年 | 24815篇 |
1994年 | 23323篇 |
1993年 | 21702篇 |
1992年 | 79498篇 |
1991年 | 76496篇 |
1990年 | 73670篇 |
1989年 | 70938篇 |
1988年 | 65953篇 |
1987年 | 64889篇 |
1986年 | 61406篇 |
1985年 | 58494篇 |
1984年 | 44341篇 |
1983年 | 37756篇 |
1982年 | 23021篇 |
1981年 | 20432篇 |
1980年 | 19153篇 |
1979年 | 41358篇 |
1978年 | 29053篇 |
1977年 | 24396篇 |
1976年 | 22875篇 |
1975年 | 24009篇 |
1974年 | 29671篇 |
1973年 | 28070篇 |
1972年 | 26248篇 |
1971年 | 24162篇 |
1970年 | 22768篇 |
1969年 | 21100篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
121.
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
122.
123.
Paul J. Devlin Brian W. McCrindle James K. Kirklin Eugene H. Blackstone William M. DeCampli Christopher A. Caldarone Ali Dodge-Khatami Pirooz Eghtesady James M. Meza Peter J. Gruber Kristine J. Guleserian Bahaaladin Alsoufi Linda M. Lambert James E. OBrien Erle H. Austin Jeffrey P. Jacobs Tara Karamlou 《The Journal of thoracic and cardiovascular surgery》2019,157(2):684-695.e8
Objective
Arch obstruction after the Norwood procedure is common and contributes to mortality. We determined the prevalence, associated factors, and practice variability of arch reintervention and assessed whether arch reintervention is associated with mortality.Methods
From 2005 to 2017, 593 neonates in the Congenital Heart Surgeons' Society Critical Left Heart Obstruction cohort underwent a Norwood procedure. Median follow-up was 3.7 years. Multivariable parametric models, including a modulated renewal analysis, were performed.Results
Of the 593 neonates, 146 (25%) underwent 218 reinterventions for arch obstruction after the Norwood procedure: catheter-based (n = 168) or surgical (n = 50) at a median age of 4.3 months (quartile 1-quartile 3, 2.6-5.7). Interdigitation of the distal aortic anastomosis was protective against arch reintervention. Development of ≥ moderate tricuspid valve regurgitation and right ventricular dysfunction at any point was associated with arch reintervention. Nonsignificant variables for arch reintervention included shunt type and preoperative aortic measurements. Surgical arch reintervention was protective against arch reintervention, but transcatheter reintervention was associated with increased reintervention. Arch reintervention was not associated with increased mortality. There was wide institutional variation in incidence of arch reintervention (range, 0-40 reinterventions per 100 years patient follow-up) and in preintervention gradient (range, 0-64 mm Hg).Conclusions
Interdigitation of the distal aortic anastomosis during the Norwood procedure decreased the risk of arch reintervention. Surgical arch reintervention is more definitive than transcatheter. Arch reintervention after the Norwood procedure is not associated with increased mortality. Serial surveillance for arch obstruction, integrated with changes in right ventricular function and tricuspid valve regurgitation, is recommended after the Norwood procedure to improve outcomes. 相似文献124.
125.
126.
127.
128.
129.
130.