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101.
Correction to Highly Selective and Potent Thiophenes
as PI3K Inhibitors with Oral Antitumor Activity
102.
Amy X Yin Gavin H Park Gwendolyn M Garnett John F Balfour 《Hawai'i Journal of Medicine & Public Health》2012,71(6):158-162
Chilaiditi syndrome is a rare condition defined by the presence of gastrointestinal symptoms associated with the radiological finding of segmental interposition of the bowel between the liver and the diaphragm. While it is infrequently indentified as a source of abdominal pain, Chilaiditi syndrome carries clinical significance as it can lead to a number of serious complications including intestinal obstruction, perforation, and ischemia. A 58-year-old woman presented with Chilaiditi syndrome immediately following colonoscopic evaluation. Conservative measures failed to alleviate the patient''s symptoms, and the patient ultimately elected to have operative management. Pexy of the cecum and ascending colon led to full resolution of her symptoms. To our knowledge, this is the first documented case of Chilaiditi syndrome iatrogenically induced by colonoscopy. Identification of this syndrome as a complication of colonoscopy and a source of post-procedural pain bears significance for providers involved in the peri-operative care of patients with factors predisposing them to the development of this condition. 相似文献
103.
A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2 下载免费PDF全文
Suzuki-Inoue K Fuller GL García A Eble JA Pöhlmann S Inoue O Gartner TK Hughan SC Pearce AC Laing GD Theakston RD Schweighoffer E Zitzmann N Morita T Tybulewicz VL Ozaki Y Watson SP 《Blood》2006,107(2):542-549
The snake venom rhodocytin has been reported to bind to integrin alpha2beta1 and glycoprotein (GP) Ibalpha on platelets, but it is also able to induce activation independent of the 2 receptors and of GPVI. Using rhodocytin affinity chromatography, we have identified a novel C-type lectin receptor, CLEC-2, in platelets that confers signaling responses to rhodocytin when expressed in a cell line. CLEC-2 has a single tyrosine residue in a YXXL motif in its cytosolic tail, which undergoes tyrosine phosphorylation upon platelet activation by rhodocytin or an antibody to CLEC-2, but not to collagen, thrombin receptor agonist peptide (TRAP), or convulxin. Tyrosine phosphorylation of CLEC-2 and other signaling proteins by rhodocytin is inhibited by the Src family kinase inhibitor PP2. Further, activation of murine platelets by rhodocytin is abolished in the absence of Syk and PLCgamma2, and partially reduced in the absence of LAT, SLP-76, and Vav1/Vav3. These findings define a novel signaling pathway in platelets whereby activation of CLEC-2 by rhodocytin leads to tyrosine phosphorylation of its cytosolic tail, binding of Syk and initiation of downstream tyrosine phosphorylation events, and activation of PLCgamma2. CLEC-2 is the first C-type lectin receptor to be found on platelets which signals through this novel pathway. 相似文献
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Leyla Y. Bustamante S. Josefin Bartholdson Cecile Crosnier Marta G. Campos Madushi Wanaguru Chea Nguon Dominic P. Kwiatkowski Gavin J. Wright Julian C. Rayner 《Vaccine》2013
The lack of an effective licensed vaccine remains one of the most significant gaps in the portfolio of tools being developed to eliminate Plasmodium falciparum malaria. Vaccines targeting erythrocyte invasion – an essential step for both parasite development and malaria pathogenesis – have faced the particular challenge of genetic diversity. Immunity-driven balancing selection pressure on parasite invasion proteins often results in the presence of multiple, antigenically distinct, variants within a population, leading to variant-specific immune responses. Such variation makes it difficult to design a vaccine that covers the full range of diversity, and could potentially facilitate the evolution of vaccine-resistant parasite strains. In this study, we investigate the effect of genetic diversity on invasion inhibition by antibodies to a high priority P. falciparum invasion candidate antigen, P. falciparum Reticulocyte Binding Protein Homologue 5 (PfRH5). Previous work has shown that virally delivered PfRH5 can induce antibodies that protect against a wide range of genetic variants. Here, we show that a full-length recombinant PfRH5 protein expressed in mammalian cells is biochemically active, as judged by saturable binding to its receptor, basigin, and is able to induce antibodies that strongly inhibit P. falciparum growth and invasion. Whole genome sequencing of 290 clinical P. falciparum isolates from across the world identifies only five non-synonymous PfRH5 SNPs that are present at frequencies of 10% or more in at least one geographical region. Antibodies raised against the 3D7 variant of PfRH5 were able to inhibit nine different P. falciparum strains, which between them included all of the five most common PfRH5 SNPs in this dataset, with no evidence for strain-specific immunity. We conclude that protein-based PfRH5 vaccines are an urgent priority for human efficacy trials. 相似文献
106.
Carly Wood Caroline Angus Jules Pretty Gavin Sandercock Jo Barton 《International journal of environmental health research》2013,23(4):311-320
This study assessed whether exercising whilst viewing natural or built scenes affected self-esteem (SE) and mood in adolescents. Twenty-five adolescents participated in three exercise tests on consecutive days. A graded exercise test established the work rate equivalent to 50% heart rate reserve for use in subsequent constant load tests (CLTs). Participants undertook two 15-min CLTs in random order viewing scenes of either natural or built environments. Participants completed Rosenberg’s SE scale and the adolescent profile of mood states questionnaire pre- and post-exercise. There was a significant main effect for SE (F(1) = 6.10; P < 0.05) and mood (F(6) = 5.29; P < 0.001) due to exercise, but no effect of viewing different environmental scenes (P > 0.05). Short bouts of moderate physical activity can have a positive impact on SE and mood in adolescents. Future research should incorporate field studies to examine the psychological effects of contact with real environments. 相似文献
107.
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110.
The role of von Willebrand factor (VWF) in thrombosis involves its binding to a number of ligands. To investigate the relative importance of these particular interactions in the thrombosis process, we have introduced mutations into murine VWF (mVWF) cDNA inhibiting VWF binding to glycoprotein (Gp) Ib, GPIIbIIIa, or to fibrillar collagen. These VWF mutants were expressed in VWF-deficient mice (VWF–/–) by using an hydrodynamic injection approach, and the mice were studied in the ferric chloride–induced injury model. Expression of the collagen and the GPIIbIIIa VWF-binding mutants in VWF–/– mice resulted in delayed thrombus growth and significantly increased vessel occlusion times compared with mice expressing wild-type (WT) mVWF (30 ± 3 minutes and 38 ± 4 minutes for the collagen and GPIIbIIIa mutants, respectively, vs 19 ± 3 minutes for WT mVWF). Interestingly, these mutants were able to correct bleeding time as efficiently as WT mVWF. In contrast, VWF–/– mice expressing the GPIb binding mutant failed to restore thrombus formation and were bleeding for as long as they were observed, confirming the critical importance of the VWF-GPIb interaction. Our observations suggest that targeting the VWF-collagen or VWF-GPIIbIIIa interactions could be an interesting alternative for new antithrombotic strategies. 相似文献