全文获取类型
收费全文 | 1530081篇 |
免费 | 97212篇 |
国内免费 | 2938篇 |
专业分类
耳鼻咽喉 | 21154篇 |
儿科学 | 47526篇 |
妇产科学 | 42094篇 |
基础医学 | 208727篇 |
口腔科学 | 41542篇 |
临床医学 | 125755篇 |
内科学 | 296790篇 |
皮肤病学 | 31108篇 |
神经病学 | 124036篇 |
特种医学 | 63032篇 |
外国民族医学 | 435篇 |
外科学 | 241574篇 |
综合类 | 33888篇 |
现状与发展 | 6篇 |
一般理论 | 438篇 |
预防医学 | 110716篇 |
眼科学 | 34254篇 |
药学 | 110893篇 |
3篇 | |
中国医学 | 3639篇 |
肿瘤学 | 92621篇 |
出版年
2018年 | 34752篇 |
2017年 | 27951篇 |
2016年 | 31808篇 |
2015年 | 13078篇 |
2014年 | 17819篇 |
2013年 | 26425篇 |
2012年 | 40395篇 |
2011年 | 56883篇 |
2010年 | 39994篇 |
2009年 | 32454篇 |
2008年 | 54920篇 |
2007年 | 61331篇 |
2006年 | 38192篇 |
2005年 | 39219篇 |
2004年 | 39714篇 |
2003年 | 40179篇 |
2002年 | 37371篇 |
2001年 | 64113篇 |
2000年 | 66067篇 |
1999年 | 55684篇 |
1998年 | 14944篇 |
1997年 | 13794篇 |
1996年 | 13129篇 |
1995年 | 12419篇 |
1994年 | 11680篇 |
1992年 | 42923篇 |
1991年 | 41471篇 |
1990年 | 40749篇 |
1989年 | 39702篇 |
1988年 | 37087篇 |
1987年 | 36532篇 |
1986年 | 35012篇 |
1985年 | 33221篇 |
1984年 | 24899篇 |
1983年 | 21127篇 |
1982年 | 12754篇 |
1981年 | 11598篇 |
1979年 | 24004篇 |
1978年 | 17132篇 |
1977年 | 14854篇 |
1976年 | 13448篇 |
1975年 | 15276篇 |
1974年 | 18118篇 |
1973年 | 17574篇 |
1972年 | 16815篇 |
1971年 | 15721篇 |
1970年 | 14952篇 |
1969年 | 14388篇 |
1968年 | 13491篇 |
1967年 | 12027篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
61.
E. M. Peterman C. Sullivan M. F. Goody I. Rodriguez-Nunez J. A. Yoder C. H. Kim 《Infection and immunity》2015,83(1):430-440
Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death. Pseudomonas aeruginosa is an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated with P. aeruginosa are capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response to P. aeruginosa infection. sod2 is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharide in vitro, and sod2 knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections. 相似文献
62.
Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes. Circulating tumour DNA (ctDNA) is the most comprehensively studied liquid biopsy analyte in blood and can provide insight into the molecular profile and biological characteristics of individual PDAC tumours, in real-time and in advance of traditional imaging modalities. This can pave the way for identification of new therapeutic targets, novel risk variants and markers of tumour response, to supplement diagnostic screening and provide enhanced scrutiny in treatment stratification. In the roadmap towards the application of precision medicine for clinical management in PDAC, ctDNA analyses may serve a leading role in streamlining candidate biomarkers for clinical integration. In this review, we highlight recent developments in the use of ctDNA-based liquid biopsies for PDAC and provide new insights into the technical, analytical and biological challenges that must be overcome for this potential to be realised. 相似文献
63.
64.
65.
66.
67.
68.
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
69.
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70.