全文获取类型
收费全文 | 33598篇 |
免费 | 2362篇 |
国内免费 | 278篇 |
专业分类
耳鼻咽喉 | 498篇 |
儿科学 | 606篇 |
妇产科学 | 732篇 |
基础医学 | 4723篇 |
口腔科学 | 878篇 |
临床医学 | 3118篇 |
内科学 | 6543篇 |
皮肤病学 | 665篇 |
神经病学 | 2393篇 |
特种医学 | 1834篇 |
外科学 | 5234篇 |
综合类 | 452篇 |
一般理论 | 10篇 |
预防医学 | 1551篇 |
眼科学 | 765篇 |
药学 | 2905篇 |
1篇 | |
中国医学 | 286篇 |
肿瘤学 | 3044篇 |
出版年
2023年 | 194篇 |
2022年 | 442篇 |
2021年 | 856篇 |
2020年 | 464篇 |
2019年 | 781篇 |
2018年 | 865篇 |
2017年 | 686篇 |
2016年 | 809篇 |
2015年 | 1136篇 |
2014年 | 1439篇 |
2013年 | 1705篇 |
2012年 | 2541篇 |
2011年 | 2489篇 |
2010年 | 1521篇 |
2009年 | 1372篇 |
2008年 | 1972篇 |
2007年 | 1955篇 |
2006年 | 1822篇 |
2005年 | 1720篇 |
2004年 | 1569篇 |
2003年 | 1398篇 |
2002年 | 1239篇 |
2001年 | 1037篇 |
2000年 | 1001篇 |
1999年 | 788篇 |
1998年 | 289篇 |
1997年 | 258篇 |
1996年 | 239篇 |
1995年 | 201篇 |
1994年 | 172篇 |
1993年 | 145篇 |
1992年 | 364篇 |
1991年 | 270篇 |
1990年 | 284篇 |
1989年 | 264篇 |
1988年 | 230篇 |
1987年 | 179篇 |
1986年 | 161篇 |
1985年 | 130篇 |
1984年 | 122篇 |
1983年 | 99篇 |
1982年 | 78篇 |
1981年 | 72篇 |
1980年 | 64篇 |
1979年 | 96篇 |
1978年 | 76篇 |
1977年 | 67篇 |
1974年 | 67篇 |
1972年 | 59篇 |
1971年 | 65篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Nasikarn Angkasekwinai Erin H. Atkins Sofia Romero John Grieco Chien Chung Chao Wei Mei Ching 《The American journal of tropical medicine and hygiene》2014,90(4):690-696
Reliable laboratory testing is of great importance to detect Bartonella bacilliformis infection. We evaluated the sensitivity and specificity of the enzyme-linked immunosorbent assay (ELISA) using recombinant protein Pap31 (rPap31) for the detection of antibodies against B. bacilliformis as compared with immunofluorescent assay (IFA). Of the 302 sera collected between 1997 and 2000 among an at-risk Peruvian population, 103 and 34 samples tested positive for IFA-immunoglobulin G (IgG) and IFA-IgM, respectively. By using Youden''s index, the cutoff values of ELISA-IgG at 0.915 gave a sensitivity of 84.5% and specificity of 94%. The cutoff values of ELISA-IgM at 0.634 gave a sensitivity of 88.2% and specificity of 85.1%. Using latent class analysis, estimates of sensitivity and specificity of almost all the assays were slightly higher than those of a conventional method of calculation. The test is proved beneficial for discriminating between infected and non-infected individuals with the advantage of low-cost and high-throughput capability. 相似文献
992.
993.
994.
995.
996.
Celine Valant Lauren T. May Luigi Aurelio Chung Hui Chuo Paul J. White Jo-Anne Baltos Patrick M. Sexton Peter J. Scammells Arthur Christopoulos 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(12):4614-4619
The concepts of allosteric modulation and biased agonism are revolutionizing modern approaches to drug discovery, particularly in the field of G protein-coupled receptors (GPCRs). Both phenomena exploit topographically distinct binding sites to promote unique GPCR conformations that can lead to different patterns of cellular responsiveness. The adenosine A1 GPCR (A1AR) is a major therapeutic target for cardioprotection, but current agents acting on the receptor are clinically limited for this indication because of on-target bradycardia as a serious adverse effect. In the current study, we have rationally designed a novel A1AR ligand (VCP746)—a hybrid molecule comprising adenosine linked to a positive allosteric modulator—specifically to engender biased signaling at the A1AR. We validate that the interaction of VCP746 with the A1AR is consistent with a bitopic mode of receptor engagement (i.e., concomitant association with orthosteric and allosteric sites) and that the compound displays biased agonism relative to prototypical A1AR ligands. Importantly, we also show that the unique pharmacology of VCP746 is (patho)physiologically relevant, because the compound protects against ischemic insult in native A1AR-expressing cardiomyoblasts and cardiomyocytes but does not affect rat atrial heart rate. Thus, this study provides proof of concept that bitopic ligands can be designed as biased agonists to promote on-target efficacy without on-target side effects.G protein-coupled receptors (GPCRs) are the largest family of cell surface proteins and tractable drug targets (1, 2). Unfortunately, there remains a high attrition rate associated with traditional GPCR-based drug discovery that, in part, reflects an emphasis on the endogenous agonist binding (orthosteric) site as the predominant means of achieving selective GPCR drug targeting (3). Over the last decade, substantial breakthroughs have occurred in the exploitation of topographically distinct GPCR allosteric sites as a means for attaining greater selectivity, especially in those instances where there is high sequence similarity in the orthosteric site across GPCR subtypes (4–6). However, there are increasing examples where both the therapeutic effect and adverse effects are mediated by the same GPCR target (7). In these situations, the desired selectivity needs to be attained at the level of the intracellular signaling pathways linked to a given receptor subtype.GPCRs are highly dynamic proteins, fluctuating between different conformations; these conformations can be linked to different cellular outcomes (8). Thus, chemically distinct ligands, interacting with either orthosteric or allosteric sites, have the potential to stabilize different interaction networks within a GPCR to promote a subset of signaling pathways linked to the receptor at the expense of others. This phenomenon has been termed biased agonism (7, 9, 10). The overall promise of biased agonism is the ability to design GPCR ligands that selectively engage therapeutically relevant signaling pathways while sparing pathways that contribute to undesirable side effects mediated by the same target.The adenosine receptor (AR) family is an important class of physiologically and therapeutically relevant GPCRs that can benefit substantially from more selective drug targeting. Although all four AR subtypes are expressed in the mammalian heart (11, 12), the well-known protective effects of adenosine in this tissue are predominantly mediated by the adenosine A1 receptor (A1AR) subtype, especially under conditions of ischemia and reperfusion injury (13–17). Unfortunately, the transition of A1AR agonists into the clinic has been severely hindered because of high doses causing on-target bradycardia, atrioventricular block, and hypotension (13, 18). As a consequence, clinical trials of AR agonists have had limited success because of the suboptimal dose of agonist that can be used (19–22). It is possible that this problem may be overcome through the exploitation of biased agonism at the A1AR.Although no study has identified biased orthosteric A1AR ligands, we recently showed that the 2-amino-3-benzoylthiophene allosteric modulator (VCP171) could promote biased signaling in the activity of the prototypical orthosteric agonist, R(-)N6-(2-phenylisopropyl) adenosine (R-PIA) (23). Thus, we hypothesized that the rational design of a bitopic ligand (i.e., a class of hybrid molecule containing both orthosteric and allosteric pharmacophores) (24–26) may be able to achieve high efficacy and biased agonism at the A1AR in a single molecule. Herein, we report proof of concept that it is possible to use this approach as a means to dissociate on-target efficacy from on-target side effects. 相似文献
997.
Tung Nguyen Eui Seon Baek Soonshin Hwang Kyung-Ho Kim Chooryung J. Chung 《The Angle orthodontist》2019,89(3):505
This report illustrates the successful nonsurgical and nonprosthetic camouflage treatment of a skeletal Class II open bite malocclusion combined with missing mandibular first molars bilaterally. In the mandible, the second and third molars were uprighted and protracted, substituting for the missing first molars. In the maxilla, anterior bodily retraction and full-arch intrusion were achieved following premolar and second molar extraction, which also induced autorotation of the mandible. The treatment outcome and prognosis were confirmed with three-dimensional superimposition techniques, along with long-term stability. 相似文献
998.
999.
Vivien M. Hsu Lorinda Chung Laura K. Hummers Fredrick Wigley Robert Simms Marcy Bolster Rick Silver Aryeh Fischer Monique E. Hinchcliff John Varga Avram Z. Goldberg Chris T. Derk Elena Schiopu Dinesh Khanna Lee S. Shapiro Robyn T. Domsic Thomas Medsger Maureen D. Mayes Daniel Furst Mary E. Csuka Jerry A. Molitor Firas Alkassab Virginia D. Steen 《Seminars in arthritis and rheumatism》2014