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171.
Markus H Hoffmann Rudolf Hopf Birgit Niederreiter Heinz Redl Josef S Smolen Günter Steiner 《Arthritis research & therapy》2010,12(2):R41
Introduction
Pristane-induced arthritis (PIA) in the rat has been described as an animal model of inflammatory arthritis which exhibits features similar to rheumatoid arthritis in humans, such as a chronic, destructive, and symmetrical involvement of peripheral joints. However, so far little is known about the earliest inflammatory events and their influence on locomotor behaviour during the course of PIA. To investigate this issue a detailed analysis of the pathologic changes occurring during the prodromal and early stages of PIA was performed. 相似文献172.
Birgit Riepl Susanne Grässel Reiner Wiest Martin Fleck Rainer H Straub 《Arthritis research & therapy》2010,12(3):R110
Introduction
Neutrophils and monocytes play an important role in overt inflammation in chronic inflammatory joint diseases such as rheumatoid arthritis (RA). The sympathetic nervous system (SNS) inhibits many neutrophil/monocyte functions and macrophage tumor necrosis factor (TNF), but because of the loss of sympathetic nerve fibers in inflamed tissue, sympathetic control is attenuated. In this study, we focused on noradrenergic and TNF regulation of human neutrophil peptides 1-3 (HNP1-3), which are proinflammatory bactericidal α-defensins. 相似文献173.
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Dual selection pressure by drugs and HLA class I-restricted immune responses on human immunodeficiency virus type 1 protease 下载免费PDF全文
Mueller SM Schaetz B Eismann K Bergmann S Bauerle M Schmitt-Haendle M Walter H Schmidt B Korn K Sticht H Spriewald B Harrer EG Harrer T 《Journal of virology》2007,81(6):2887-2898
To determine the influence of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells on the development of drug resistance mutations in the HIV-1 protease, we analyzed protease sequences from viruses from a human leukocyte antigen class I (HLA class I)-typed cohort of 94 HIV-1-positive individuals. In univariate statistical analyses (Fisher's exact test), minor and major drug resistance mutations as well as drug-associated polymorphisms showed associations with HLA class I alleles. All correlations with P values of 0.05 or less were considered to be relevant without corrections for multiple tests. A subset of these observed correlations was experimentally validated by enzyme-linked immunospot assays, allowing the definition of 10 new epitopes recognized by CD8+ T cells from patients with the appropriate HLA class I type. Several drug resistance-associated mutations in the protease acted as escape mutations; however, cells from many patients were still able to generate CD8+ T cells targeting the escape mutants. This result presumably indicates the usage of different T-cell receptors by CD8+ T cells targeting these epitopes in these patients. Our results support a fundamental role for HLA class I-restricted immune responses in shaping the sequence of the HIV-1 protease in vivo. This role may have important clinical implications both for the understanding of drug resistance pathways and for the design of therapeutic vaccines targeting drug-resistant HIV-1. 相似文献
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Döring B Pfitzer G Adam B Liebregts T Eckardt D Holtmann G Hofmann F Feil S Feil R Willecke K 《Cell and tissue research》2007,327(2):333-342
Connexin43 (Cx43) gap-junction channels are highly abundant in intestinal smooth muscle but their functional impact has not
been studied so far. Here, we have aimed to elucidate the functional role of Cx43 in the tunica muscularis of the mouse intestine
in vivo. Transgenic mice with conditional deletion of Cx43 in smooth muscle cells (SMC) were generated. Histological investigations
by immunofluorescence analyses and organ-bath recordings to assess the contractility of intestinal tissue strips were carried
out. Measurements of gastrointestinal transit and of the visceromotor response by utilizing a standardized colorectal distension
model to quantify alterations of visceral sensory function were also performed in SMC-specific Cx43 null mice and control
littermates. Histologically, we found thickening of the tunica muscularis and a 13-fold increase of neutrophil infiltration
of the gastrointestinal wall of SMC-specific Cx43 null mice. These animals also exhibited a decrease of 29% in gastrointestinal
transit time. In contrast, the visceromotor response to a standardized colorectal distension was elevated, as was the contractility
in SMC-specific Cx43 null mice, compared with controls. Thus, SMC-specific ablation of Cx43 in mice leads to morphological
and functional alterations of the intestinal tunica muscularis, to gastrointestinal motor dysfunction and to altered visceral
sensory function.
This study was supported by a grant from the German Research Association (Wi 270/25-1,2) to K.W. and in part by the IFORES
program of the University Hospital, Essen, Germany. 相似文献