全文获取类型
收费全文 | 10015篇 |
免费 | 788篇 |
国内免费 | 288篇 |
专业分类
耳鼻咽喉 | 12篇 |
儿科学 | 443篇 |
妇产科学 | 66篇 |
基础医学 | 2084篇 |
口腔科学 | 30篇 |
临床医学 | 991篇 |
内科学 | 2339篇 |
皮肤病学 | 746篇 |
神经病学 | 188篇 |
特种医学 | 101篇 |
外科学 | 941篇 |
综合类 | 1738篇 |
预防医学 | 212篇 |
眼科学 | 78篇 |
药学 | 616篇 |
3篇 | |
中国医学 | 470篇 |
肿瘤学 | 33篇 |
出版年
2024年 | 10篇 |
2023年 | 167篇 |
2022年 | 207篇 |
2021年 | 319篇 |
2020年 | 316篇 |
2019年 | 357篇 |
2018年 | 322篇 |
2017年 | 304篇 |
2016年 | 327篇 |
2015年 | 324篇 |
2014年 | 554篇 |
2013年 | 849篇 |
2012年 | 484篇 |
2011年 | 543篇 |
2010年 | 432篇 |
2009年 | 451篇 |
2008年 | 466篇 |
2007年 | 513篇 |
2006年 | 468篇 |
2005年 | 395篇 |
2004年 | 421篇 |
2003年 | 329篇 |
2002年 | 328篇 |
2001年 | 270篇 |
2000年 | 233篇 |
1999年 | 210篇 |
1998年 | 174篇 |
1997年 | 152篇 |
1996年 | 121篇 |
1995年 | 124篇 |
1994年 | 122篇 |
1993年 | 123篇 |
1992年 | 100篇 |
1991年 | 84篇 |
1990年 | 91篇 |
1989年 | 53篇 |
1988年 | 58篇 |
1987年 | 43篇 |
1986年 | 40篇 |
1985年 | 41篇 |
1984年 | 41篇 |
1983年 | 22篇 |
1982年 | 31篇 |
1981年 | 20篇 |
1980年 | 16篇 |
1979年 | 12篇 |
1978年 | 13篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1975年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 500 毫秒
71.
系统性红斑狼疮临床特征与HLA—DR,DQ基因的相关研究 总被引:2,自引:0,他引:2
采用聚合酶链反应结合顺序特异物寡核苷酸(PCR/SSO)探针杂交方法对HLA-DR,DQ亚区作DNA分型,分析了系统性红斑狼疮(SLE)的各种临床特征与HLA-DR、DQ基因的关联,结果发现汉族SLE中肾脏损害与DR2相关,而与DR4呈负相关,口、鼻腔粘膜溃疡与DR12相关,未发现SLE的其他临床特征与DR、DQ基因有关,发病年龄小于35a者,DR2,DQ6阳性率高,而DR3则多见于发病年龄大于3 相似文献
72.
Sequence analysis of the germ-line VH gene corresponding to a nephritogenic antibody in MRL/lpr lupus mice. 总被引:1,自引:0,他引:1 下载免费PDF全文
In order to investigate the genetic origin of nephritogenic antibodies in MRL/Mp-lpr/lpr (MRL/lpr) lupus mice, we isolated the germ-line heavy chain variable region (VH) gene corresponding to the nephritogenic antibody, B1, derived from an unmanipulated MRL/lpr mouse. Injection of this antibody into C.B-17/Icr-scid/scid mice resulted in the generation of wire loop-like glomerular lesions resembling those of lupus nephritis. Nucleotide sequences of this germ-line VH gene showed no replacement mutation in the VH region of the B1 antibody. Furthermore, this gene was identical to that found in the C3H/HeJ-lpr/lpr strain of mice. Our results suggest that germ-line VH genes can encode nephritogenic antibodies without somatic mutation, even in a mouse strain not prone to lupus. 相似文献
73.
Stress or heat-shock proteins may be involved in the initiation and perpetuation of autoimmune diseases. In order to investigate a possible role of autoantibodies against the 70-kD family of heat-shock proteins in systemic lupus erythematosus (SLE), sera of SLE patients and healthy subjects were tested for the presence of IgG and IgM antibodies to 70-kD class proteins. These proteins were purified by affinity chromatography on ATP-agarose and used in Western blotting studies. The data obtained revealed that antibodies to the 72-kD and the 73-kD heat-shock proteins occurred with similar frequencies both in healthy subjects and SLE patients. Thus, approximately 20% of the sera in each group contained IgG antibodies, and IgM antibodies were detected in about 30% of the sera tested. Moreover, in SLE patients no association between the occurrence and litre of these antibodies and disease activity was found. These data suggest that antibodies to the 70-kD class heat-shock proteins are naturally occurring and argue therefore against an involvement of these antibodies in the pathogenesis of SLE. 相似文献
74.
Autoantibodies against cyclophilin in systemic lupus erythematosus and Lyme disease. 总被引:2,自引:0,他引:2 下载免费PDF全文
A Kratz M W Harding J Craft C G Mackworth-Young R E Handschumacher 《Clinical and experimental immunology》1992,90(3):422-427
Autoantibodies against cyclophilin, a cyclosporin A binding protein, were detected in sera of 29 of 46 (63%) patients with systemic lupus erythematosus and 14 of 40 (35%) Lyme disease patients. The antibodies are directed against the denatured form of both the major and minor isoform of cyclophilin and can be demonstrated in Western blots. Some first-degree relatives of lupus patients also express these antibodies. They are specific for cyclophilin and are not the consequence of hypergammaglobulinaemia. Four monoclonal IgM antibodies from a patient with lepromatous leprosy also bound to cyclophilin. The generation of these antibodies may be of special interest because they are against a protein involved in the control of the immune system not known to be directly associated with DNA or RNA. 相似文献
75.
R. -M. Jolidon MD H. Knecht L. Humair A. de Torrente 《Journal of molecular medicine (Berlin, Germany)》1991,69(8):340-344
Summary A young man who had suffered several episodes of deep-vein thrombosis of the legs since the age of 20 had a myocardial infarction at the age of 33, at which time both a prolonged partial thromboplastin time (PTT), compatible with a lupus anticoagulant (LA), and decreased fibrinolytic capacity (FC) were found.His sister presented with deep-vein thrombosis of a leg and subsequent pulmonary embolism when she was 18 years old. She had a miscarriage three years later and developed a hemolytic-uremic syndrome at the age of 35. The PT and FC were normal. Laboratory investigations of the parents revealed positive antinuclear antibodies in the mother's serum but no anomaly in the father.This study suggests a familial tendency to develop autoimmune disorders associated with LA and thromboembolic complications related to decreased FC. 相似文献
76.
An increased frequency of autoantibody-inducing CD4+ T cells in pre-diseased lupus-prone mice 总被引:1,自引:0,他引:1
Pathogenic autoantibody production in murine models of lupus is dependent on autoreactive CD4+ helper T cells. However, the mechanisms which permit the selection and maintenance of this autoantibody-inducing CD4+ T-cell repertoire are currently unknown. We hypothesized that the peripheral CD4+ T-cell repertoire of lupus-prone mice was enriched with autoantibody-inducing specificities. To test this, we utilized the splenic focus assay to determine if pre-diseased lupus-prone (NZB x NZW)F(1) mice have an elevated frequency of autoreactive CD4+ T lymphocytes capable of supporting autoantibody production. The splenic focus limiting dilution assay permits anti-nuclear antibodies to be generated from contact-dependent T-B interactions in vitro. We show that young, pre-diseased lupus-prone mice have an elevated frequency of autoantibody-inducing CD4+ T cells. Interestingly, these autoantibody-inducing CD4+ T-cell responses are also present in the thymus. Therefore, an elevated frequency of autoantibody-inducing CD4+ T cells predisposes lupus-prone mice to the development of autoantibodies. 相似文献
77.
用双抗体夹心ELISA检测66例SIE病人血清叽sIL-2R水平,SLE病人显著高于正常人,疾病活动期高于非活动期。血清sIL-2R水平与ANA、抗ds-DNA抗体、抗Sm、SS-A、SS-B抗体无关,而与SLE患者的发热、贫血、白细胞减少、关节受累及肾脏损害相关,且与SLE疾病活动性和ESR成正相关,与补体C_3、C_4和CH_(50)成负相关。提示血清sIL-2R水平是监测SLE疾病活动性的一个良好指标。 相似文献
78.
C Morland J Michael D Adu T Kizaki A J Howie A Morgan N A Staines 《Clinical and experimental immunology》1991,83(1):126-132
The effect of the administration of a xenogeneic anti-idiotype antibody (anti-Id33) to a cross-reactive idiotype (Id33) present on anti-dsDNA antibody was examined in 6-week-old (NZB/NZW) F1 (BWF1) female mice. The administration of anti-Id33 led to a transient reduction in immunoglobulins expressing Id33, followed by a rise at 30 and 34 weeks that was significantly higher than in untreated mice (P less than 0.05). Likewise, anti-dsDNA antibody levels were significantly higher at 10 and 18 weeks than in untreated mice (P less than 0.01). No differences were seen in survival to 40 weeks, proteinuria or the severity of glomerulonephritis. Concurrent administration of cyclosporin A (CyA) with anti-Id33 markedly ameliorated glomerular injury and proteinuria and improved survival. By contrast, glomerular injury, proteinuria and survival were worse in mice treated with cyclophosphamide plus anti-Id33, compared with untreated mice. Neither CyA nor cyclophosphamide treatment, when given with anti-Id33 altered serum levels of anti-dsDNA, anti-ssDNA or Id33+ immunoglobin, compared with untreated mice. The different effects of CyA and cyclophosphamide on T lymphocytes and their discrepant effects on glomerular injury when given with anti-Id33 in this model lead us to postulate a role for T lymphocytes in the glomerular injury of BWF1 lupus. 相似文献
79.
M VAN GRIENSVEN E C BERGIJK J J BAELDE E DE HEER J A BRUIJN 《Clinical and experimental immunology》1997,107(2):254-260
In patients with systemic lupus erythematosus, the female-to-male ratio is as high as 10:1. Sex hormones are thought to play a role in this difference in susceptibility. In a previous study, we demonstrated a high susceptibility of female mice to the development of glomerulonephritis after induction of chronic graft-versus-host disease (GVHD), compared with male mice. In order to unravel further this gender-related difference (C57Bl/10*DBA/2)F1 hybrid mice were either castrated or ovariectomized and treated with 17β-ethinyloestradiol or testosterone-decanoate preceding the induction of chronic GVHD. Testosterone-decanoate reduced significantly the development of albuminuria in females. In contrast, proteinuria of 17β-ethinyloestradiol-treated female mice was in the same range as that of sham-operated mice. Autoantibody levels against glomerular basement membrane, renal tubular epithelium, dsDNA and ssDNA, as determined by ELISA, were higher in 17β-ethinyloestradiol-treated female mice than in all other groups. Immunofluorescence studies showed the presence of immunoglobulin and complement deposits in glomeruli of all animals, without significant differences between the experimental groups. Our findings confirm earlier observations, in that testosterone-decanoate is shown to be an inhibitory compound, whereas 17β-ethinyloestradiol has stimulating properties in autoimmunity. Moreover, our results show for the first time differential hormonal effects on autoantibody levels and proteinuria in experimental lupus nephritis. 相似文献
80.
Sophie Kontouzov Alban Cabrespines Zahir Amoura Henri Chabre Chantal Lotton Jean-Franois Bach 《European journal of immunology》1996,26(2):472-486
In the present study, we sought evidence for a surface nucleosome receptor in the fibroblastic cell line CV-1, and questioned whether anti-double-stranded (ds)DNA and/or anti-histone autoantibodies could recognized and influence the fate of cell surface-bound nucleosomes. 125I-labeled mononucleosomes were shown to bind to the cell layer in a specific, concentration-dependent and a saturable manner. Scatchard analysis revealed the presence of two binding sites: a high-affinity site with a Kd of ~ 7nM and a low-affinity site (Kd ~ 400 nM) with a high capacity of 9 × 107 sites. Visualization of bound mononucleosomes by fluorescence revealed staining on both the cell surface and the extracellular matrix (ECM). Purified mononucleosome-derived dsDNA (180–200 bp) was found to compete for binding of 125I-mononucleosomes on the low-affinity site, to stain exclusively the ECM in immunofluorescence, and to precipitate three specific proteins of 43, 180 and 240 kDa from 125-I-labeled cell lysates. Nucleosomes were found to precipitate not only the 180-kDa dsDNA-reactive component, but also a unique protein of 50 kDa, suggesting that this protein is a cell surface receptor for nucleosomes on these fibroblasts. Once bound on the cell surface, mononucleosomes were recognized and secondarily complexed by lupus anti-dsDNA or anti-histone antibodies (i.e. anti-nucleosome antibodies), thus forming immune complexes in situ. The presence of these complexing auto-antibodies was found dramatically to enhance the kinetics of mononucleosome internalization. Following the internalization of the nucleosome-anti-nucleosome complexes by immunofluorescence, we observed the formation of vesicles at the edge of the cells by 5–10 min which moved toward the perinuclear region by 20–30 min. By means of double-fluorescence labeling and proteolytic treatment, these fluorescent vesicles were shown to be in the cytoplasm, suggesting true endocytosis of nucleosome-anti-nucleosome immune complexes. As shown by confocal microscopy, at no stage of this endocytic process was there any indication that coated pits or coated vesicles participated. Co-distribution of the endocytic vesicles with regions rich in actin filaments and inhibition of endocytosis of nucleosome-anti-nucleosome complexes by disruption of the micro-filament network with cytochalasin D suggest a mechanism mediated by the cytoskeleton. Taken together, our data provide evidence for the presence of a surface nucleosome receptor. We also show that anti-dsDNA and anti-histone antibodies can form nucleosome-anti-nucleosome immune complexes in situ at the cell surface, and thus dramatically enhance the kinetics of nucleosome endocytosis. 相似文献