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91.
Maria Benito de Valle Tobias Müller Einar Björnsson Morgane Otten Martin Volkmann Olaf Guckelberger Bertram Wiedenmann Riadh Sadik Eckart Schott Mats Andersson Thomas Berg Björn Lindkvist 《Digestive and liver disease》2014,46(10):903-908
Background
Elevated IgG4 levels have been reported among patients with primary sclerosing cholangitis. Epidemiological data has only been provided from tertiary centres.Aims
To investigate the prevalence of elevated IgG4 levels and to compare prognosis between patients with and without elevated IgG4 levels in serum in two European cohorts of patients with primary sclerosing cholangitis.Methods
Serum IgG4-levels were measured in a consecutive series of patients from Berlin, and retrospectively collected in a population-based cohort from Sweden (total N = 345). Cox's proportional hazard analysis was used to calculate relative risks for liver-related death or liver transplantation and cholangiocarcinoma.Results
Elevated IgG4 values were demonstrated in 10% of patients. A previous history of pancreatitis, combined intra- and extrahepatic biliary involvement and jaundice were independently associated with elevated IgG4 in multivariate analysis. IgG4 status was not associated with an increased risk for the combined endpoint liver-related death or liver transplantation or cholangiocarcinoma.Conclusion
The prevalence of elevated IgG4 values among European patients with primary sclerosing cholangitis is similar to what previously has been reported from the United States. Elevated IgG4 was not associated with an increased risk of liver transplantation or liver-related death or cholangiocarcinoma. 相似文献92.
Jagadeesh Bayry Audrey Beaussart Yves F. Dufrêne Meenu Sharma Kushagra Bansal Olaf Kniemeyer Vishukumar Aimanianda Axel A. Brakhage Srini V. Kaveri Kyung J. Kwon-Chung Jean-Paul Latgé Anne Beauvais 《Infection and immunity》2014,82(8):3141-3153
In Aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin biosynthesis. Melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. In the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface. Melanin as such was immunologically inert; however, deletion mutant conidia with modified surfaces could activate human dendritic cells and the subsequent cytokine production in contrast to the wild-type conidia. Cell surface defects were rectified in the conidia mutated in downstream melanin biosynthetic pathway, and maximum immune inertness was observed upon synthesis of vermelone onward. These observations suggest that although melanin as such is an immunologically inert material, it confers virulence by facilitating proper formation of the A. fumigatus conidial surface. 相似文献
93.
Sabine Rauch Portia Gough Hwan Keun Kim Olaf Schneewind Dominique Missiakas 《Infection and immunity》2014,82(11):4889-4898
The risk for Staphylococcus aureus bloodstream infection (BSI) is increased in immunocompromised individuals, including patients with hematologic malignancy and/or chemotherapy. Due to the emergence of antibiotic-resistant strains, designated methicillin-resistant S. aureus (MRSA), staphylococcal BSI in cancer patients is associated with high mortality; however, neither a protective vaccine nor pathogen-specific immunotherapy is currently available. Here, we modeled staphylococcal BSI in leukopenic CD-1 mice that had been treated with cyclophosphamide, a drug for leukemia and lymphoma patients. Cyclophosphamide-treated mice were highly sensitive to S. aureus BSI and developed infectious lesions lacking immune cell infiltrates. Virulence factors of S. aureus that are key for disease establishment in immunocompetent hosts—α-hemolysin (Hla), iron-regulated surface determinants (IsdA and IsdB), coagulase (Coa), and von Willebrand factor binding protein (vWbp)—are dispensable for the pathogenesis of BSI in leukopenic mice. In contrast, sortase A mutants, which cannot assemble surface proteins, display delayed time to death and increased survival in this model. A vaccine with four surface antigens (ClfA, FnBPB, SdrD, and SpAKKAA), which was identified by genetic vaccinology using sortase A mutants, raised antigen-specific immune responses that protected leukopenic mice against staphylococcal BSI. 相似文献
94.
95.
LE Quenee TM Hermanas N Ciletti H Louvel NC Miller D Elli B Blaylock A Mitchell J Schroeder T Krausz J Kanabrocki O Schneewind 《The Journal of infectious diseases》2012,206(7):1050-1058
Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv(-/-)) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv(-/-) mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv(-/-) mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines. 相似文献
96.
van den Heuvel MP Kahn RS Goñi J Sporns O 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(28):11372-11377
Network studies of human brain structural connectivity have identified a specific set of brain regions that are both highly connected and highly central. Recent analyses have shown that these putative hub regions are mutually and densely interconnected, forming a "rich club" within the human brain. Here we show that the set of pathways linking rich club regions forms a central high-cost, high-capacity backbone for global brain communication. Diffusion tensor imaging (DTI) data of two sets of 40 healthy subjects were used to map structural brain networks. The contributions to network cost and communication capacity of global cortico-cortical connections were assessed through measures of their topology and spatial embedding. Rich club connections were found to be more costly than predicted by their density alone and accounted for 40% of the total communication cost. Furthermore, 69% of all minimally short paths between node pairs were found to travel through the rich club and a large proportion of these communication paths consisted of ordered sequences of edges ("path motifs") that first fed into, then traversed, and finally exited the rich club, while passing through nodes of increasing and then decreasing degree. The prevalence of short paths that follow such ordered degree sequences suggests that neural communication might take advantage of strategies for dynamic routing of information between brain regions, with an important role for a highly central rich club. Taken together, our results show that rich club connections make an important contribution to interregional signal traffic, forming a central high-cost, high-capacity backbone for global brain communication. 相似文献
97.
98.
Kynast-Wolf G Wakilzadeh W Coulibaly B Schnitzler P Traoré C Becher H Müller O 《Acta tropica》2012,123(2):117-122
Malaria blood-stage vaccines are in an early phase of clinical development with MSP1 being a major antigen candidate. There are limited data on the protective efficacy of antibodies against subunits of MSP1 in the malaria endemic areas of sub-Saharan Africa. This prospective cohort study was nested into a large insecticide-treated mosquito net (ITN) trial during which neonates were individually randomised to ITN protection from birth vs. protection from month six onwards in rural Burkina Faso. A sub sample of 120 children from three villages was followed for 10 months with six measurements of MSP1(42) antibodies (ELISA based on recombinant 42kDa fragment) and daily assessment of malaria episodes. Time to the next malaria episode was determined in relation to MSP1(42) antibody titres. MSP1(42) antibody titres were dependent on age, season, ITN-group, number of previous malaria episodes and parasitaemia. There were no significant differences in time until the next malaria episode in children with low compared to children with high MSP1(42) antibody titres at any point in time (101 vs. 97 days in May, p=0.6; 58 vs. 84 days in September, p=0.3; 144 vs. 161 days in March, p=0.5). The findings of this study support the short-lived nature of the humoral immune response in infants of malaria endemic areas. The study provides no evidence for antibodies against a subunit of MSP1 being protective against new malaria episodes in infants. 相似文献
99.
100.
Trends in incidence,tumour sites and tumour stages of oral and pharyngeal cancer in Northern Germany
Hertrampf K Wiltfang J Katalinic A Timm O Wenz HJ 《Journal of cancer research and clinical oncology》2012,138(3):431-437