全文获取类型
收费全文 | 374659篇 |
免费 | 31830篇 |
国内免费 | 13940篇 |
专业分类
耳鼻咽喉 | 2729篇 |
儿科学 | 7404篇 |
妇产科学 | 4691篇 |
基础医学 | 63305篇 |
口腔科学 | 6690篇 |
临床医学 | 26024篇 |
内科学 | 65883篇 |
皮肤病学 | 5800篇 |
神经病学 | 28620篇 |
特种医学 | 8007篇 |
外国民族医学 | 105篇 |
外科学 | 27247篇 |
综合类 | 48820篇 |
现状与发展 | 48篇 |
一般理论 | 6篇 |
预防医学 | 18863篇 |
眼科学 | 4140篇 |
药学 | 51771篇 |
64篇 | |
中国医学 | 13959篇 |
肿瘤学 | 36253篇 |
出版年
2024年 | 947篇 |
2023年 | 6194篇 |
2022年 | 13259篇 |
2021年 | 16771篇 |
2020年 | 13282篇 |
2019年 | 13608篇 |
2018年 | 12937篇 |
2017年 | 12680篇 |
2016年 | 12545篇 |
2015年 | 14770篇 |
2014年 | 21704篇 |
2013年 | 24321篇 |
2012年 | 21917篇 |
2011年 | 25664篇 |
2010年 | 21544篇 |
2009年 | 21298篇 |
2008年 | 20367篇 |
2007年 | 18530篇 |
2006年 | 16695篇 |
2005年 | 14380篇 |
2004年 | 12338篇 |
2003年 | 10667篇 |
2002年 | 8449篇 |
2001年 | 7142篇 |
2000年 | 5972篇 |
1999年 | 5443篇 |
1998年 | 4736篇 |
1997年 | 4377篇 |
1996年 | 3879篇 |
1995年 | 3410篇 |
1994年 | 3048篇 |
1993年 | 2552篇 |
1992年 | 2186篇 |
1991年 | 1981篇 |
1990年 | 1665篇 |
1989年 | 1364篇 |
1988年 | 1263篇 |
1987年 | 1010篇 |
1986年 | 965篇 |
1985年 | 1980篇 |
1984年 | 2187篇 |
1983年 | 1543篇 |
1982年 | 1637篇 |
1981年 | 1376篇 |
1980年 | 1155篇 |
1979年 | 1000篇 |
1978年 | 807篇 |
1977年 | 638篇 |
1976年 | 706篇 |
1975年 | 508篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Molecular and biological analysis of echovirus 9 strain isolated from a diabetic child 总被引:2,自引:0,他引:2
Paananen A Ylipaasto P Rieder E Hovi T Galama J Roivainen M 《Journal of medical virology》2003,69(4):529-537
The full-length infectious cDNA clone was constructed and sequenced from the strain DM of echovirus 9, which was recently isolated from a 6-week-old child at the clinical onset of type 1 diabetes. Parallel with the isolate DM, the full-length infectious cDNA clone of the prototype strain echovirus 9 Barty (Barty-INF), was constructed and sequenced. Genetic relationships of the sequenced echo 9 viruses to the other members of the human enterovirus type B species were studied by phylogenetic analyses. Comparison of capsid protein sequences showed that the isolate DM was closely related to both prototype strains: Hill and Barty-INF. The only exception was the inner capsid protein VP4 where serotype specificity was not evident and the isolate DM clustered with the strain Hill and the strain Barty-INF with echovirus 30 Bastianni. Likewise, the nonstructural protein coding region, P2P3, of isolate DM was more similar to strain Hill than to strain Barty-INF. However, like echovirus 9 Barty, the isolate DM contained the RGD-motif in the carboxy terminus of capsid protein VP1. By blocking experiments using an RGD-containing peptide and a polyclonal rabbit antiserum to the alpha(v)beta(3)-integrin, it was shown that this molecule works as a cellular receptor for isolate DM. By using primary human islets, it was shown that the isolate DM is capable of infecting insulin-producing beta-cells like the corresponding prototype strains did. However, only isolate DM was clearly cytolytic for beta-cells. The infectious clones that were made allow further investigations of the molecular features responsible for the diabetogenicity of the isolate DM. 相似文献
992.
Intraglomerular expressions of IL-1 alpha and platelet-derived growth factor (PDGF-B) mRNA in experimental immune complex-mediated glomerulonephritis. 下载免费PDF全文
Y Akai M Iwano Y Kitamura H Shiiki Y Dohi K Dohi T Moriyama K Yonemasu 《Clinical and experimental immunology》1994,95(1):29-34
Acute lung injury frequently develops following haemorrhage, and is characterized by increased proinflammatory cytokine levels and massive neutrophil accumulation in the lung. Blood loss produces rapid increases in tumour necrosis factor-alpha (TNF-alpha) mRNA expression among pulmonary cell populations which precede the development of lung injury. In order to examine the role of TNF-alpha in producing acute inflammatory lung injury, we treated mice following haemorrhage and resuscitation with a TNF antagonist, composed of soluble dimeric human p80 TNF receptor linked to the Fc region of human IgG1 (sTNFR:Fc). Therapy with sTNFR:Fc prevented the post-haemorrhage increases in circulating and pulmonary TNF-alpha levels normally found following blood loss. Administration of sTNFR:Fc also diminished the increase in IL-1 beta, IL-6, TNF-alpha and interferon-gamma (IFN-gamma) mRNA normally found in the lungs following haemorrhage. However, therapy with sTNFR:Fc was not associated with improvement in the histologic parameters of post-haemorrhage lung injury, such as neutrophil infiltration and interstitial oedema. In contrast to the effects of sTNFR:Fc on cytokine mRNA levels among intraparenchymal pulmonary mononuclear cells, such therapy following haemorrhage was associated with increased amounts of mRNA for TNF-alpha among peripheral blood mononuclear cells, as well as increased IFN-gamma titres in serum and bronchoalveolar lavage (BAL) specimens. These results indicate that therapy with sTNFR:Fc in the post-haemorrhage period, although capable of decreasing proinflammatory cytokine expression in the lungs, does not prevent the development of acute lung injury in this setting. 相似文献
993.
We have used an antibody against a TGFβ peptide fragment to localize this growth factor in the early chick embryo from laying to the ten-somite stage of development. Western blotting showed that the antibody reacted with both mammalian TGFβ1 and chicken TGFβ3. By immunocytochemistry we find that at the earliest developmental stage (stage X of Eyal-Giladi and Kochav) immunoreactivity to this antibody is primarily located in the cells of the area opaca and marginal zone, as well as in the most peripheral edge cells of the blastoderm. The yolk is non-reactive, except in a highly localized region subjacent to the edge cells. This pattern persists at stage XII, and at both stages individual isolated cells in the epiblast and hypoblast are also reactive. By the time to gastrulation, reactivity in the epiblast is polarized to the ventral extremity of the cells, and again some isolated cells in this layer are intensely immunoreactive. At this stage also, the endoderm cells, particularly those underlying the primitive streak, are positive, as are the mesoderm cells lateral to the streak. At somite stages, the neuroepithelium is not reactive but the ectoderm lateral to it is strongly positive. At the caudal primitive streak levels of early somite embryos, the ectoderm and endoderm are immunoreactive while the mesoderm loses the reactivity it showed at the early gastrulation stages. The neuroepithelial cells later show reactivity at their apical poles, and, as at the earlier stages, individual cells show intense labelling. These results indicate that TGFβ1 and/or TGFβ3 immunoreactivity is developmentally regulated from very early stages of morphogenesis in the chick, and together with data from earlier functional studies, suggest that this factor has roles in embryonic axis formation and in blastoderm expansion. © 1994 Wiley-Liss, Inc. 相似文献
994.
Analysis of cytokine profiles in synovial T cell clones from chlamydial reactive arthritis patients: predominance of the Th1 subset. 总被引:11,自引:1,他引:11 下载免费PDF全文
A K Simon E Seipelt P Wu B Wenzel J Braun J Sieper 《Clinical and experimental immunology》1993,94(1):122-126
Subpopulations of human T cells (Th0, Th1 and Th2) can be distinguished by their cytokine-secretion pattern. Evidence is increasing from other studies that the outcome of a human disease may depend on the subpopulation of T cells that predominates at the site of inflammation. Reactive arthritis serves as a useful model of chronic inflammatory diseases, because the triggering antigen can be identified. Using this triggering antigen we raised 33 T cell clones reactive with Chlamydia trachomatis and 25 T cell clones that were not reactive, all from the synovial fluid of two patients suffering from Chlamydia-induced arthritis. Their cytokine secretion patterns for interferon-gamma (IFN-gamma), IL-2 and IL-4 were analysed, as also were mRNAs for IFN-gamma and IL-10 by in situ hybridization. Out of the 33 antigen-reactive clones 23 showed a Th1 pattern with IFN-gamma but not IL-4 secretion, while the remaining 10 exhibited a Th0 pattern. The clones that did not react with Chlamydia expressed all patterns of cytokine secretion, including a Th2 pattern, thus providing a control population that excludes bias in the sampling procedure. CD4 and CD8 clones displayed a similar cytokine-secretion pattern. In addition this study demonstrates for the first time the expression of IL-10 mRNA in T cell clones derived from synovial fluid, and this was not confined to the Th2 subset. The Th1 response that Chlamydia provoke can be regarded as appropriate for such an obligate intracellular pathogen. 相似文献
995.
APO-1(CD95)-dependent and -independent antigen receptor-induced apoptosis in human T and B cell lines 总被引:3,自引:0,他引:3
Peter Marcus E.; Dhein Jens; Ehret Andreas; Hellbardt Stefan; Walczak Henning; Moldenhauer Gerhard; Krammer Peter H. 《International immunology》1995,7(11):1873-1884
Certain B and T cell lines respond to activation signals, e.g.through the antigen receptor, by undergoing apoptotlc cell death.In T cells it has been recently shown that TCR-mediated apoptosisinvolves APO-1/Fas (CD95) receptor-ligand interaction. To investigatewhether the TCR-CD3 complex can trigger alternative apoptosispathways we generated subclones of the T cell line Jurkat whichwere completely resistant towards APO-1-mediated apoptosis.These JurkatR cells differed phenotypically from sensitive parentalJurkatS cells only by the lack of APO-1 protein expression.Although JurkatR cells responded normally to anti-CD3 stimulationby expression of APO-1 ligand they failed to undergo anti-CD3-inducedapoptosis. Thus, in Jurkat cells APO-1 -mediated apoptosis wasthe main, and might be the only, mechanism for anti-CD3-inducedcell death. However, BL-60 B cells, highly sensitive to anti-IgM-inducedapoptosis, did not use the APO-1 receptor-ligand system becausethey failed to express APO-1 ligand mRNA. Taken together, ourresults suggest that malignant T and B cell lines may use APO-1receptor-ligand-dependent and -independent antigen receptor-inducedapoptosis pathways respectively. Similarly, differential pathwaysmay be used by T and B cell subsets. 相似文献
996.
Anti-inflammatory activity of salmeterol: down-regulation of cytokine production. 总被引:6,自引:0,他引:6 下载免费PDF全文
L Sekut B R Champion K Page J A Menius Jr K M Connolly 《Clinical and experimental immunology》1995,99(3):461-466
Elevation of intracellular cAMP levels has been shown previously to inhibit cytokine secretion by various cell types in vitro. Since salmeterol is a beta 2-agonist which activates adenylate cyclase, its ability to inhibit cytokine production was evaluated. Though salmeterol, and the related drug albuterol, did not inhibit IL-1 beta production in vitro, both drugs did inhibit tumour necrosis factor-alpha (TNF-alpha) secretion by lipopolysaccharide (LPS)-activated THP-1 cells with similar IC50s of approximately 0.1 microM. This inhibition was effectively reversed by the beta 2-antagonist oxprenolol, indicating that the inhibition was mediated through the beta 2-adrenergic receptor. A strikingly different reactivity profile was seen with T cells. Salmeterol was able to inhibit the activation of both mouse and human T cells, as measured by proliferation and IL-2 secretion in response to anti-CD3 antibody, whereas albuterol was completely inactive in these assays. This T cell inhibition by salmeterol was about 10-fold less potent than that for TNF-alpha production, and was not reversed by a beta 2-antagonist, indicating that a different mechanism was involved in the effect of salmeterol on T cells. Paralleling the TNF-alpha inhibitory activity in vitro, oral dosing of salmeterol and albuterol inhibited LPS-induced increase in murine serum TNF level in vivo, with ED50s of approximately 0.1 mg/kg. This inhibition could be abrogated by dosing orally with the beta-blocker propranolol. The long-acting pharmacological profile of salmeterol was apparent in that it maintained its efficacy for 3 h, while albuterol had a much shorter duration of action. Salmeterol also had some protective effects in the galactosamine/LPS model of endotoxic shock, which is dependent upon TNF-alpha production. Though salmeterol inhibited serum TNF-alpha levels by up to 94% in this assay, it protected less than 50% of the animals from the lethal effects of the LPS/galactosamine mixture. This observation suggests that functional levels of TNF-alpha localized in tissues may not be accurately reflected by serum levels. 相似文献
997.
人FascDNA的克隆及其在大肠杆菌中表达的研究 总被引:1,自引:1,他引:1
为获得高质量及充足的Fas蛋白,采用PCR技术调整Fas基因的开放阅读框架,使之与生物素化蛋白基因阅读框架一致;缺失了FascDNA基因的起始密码子并增加一个大肠杆菌偏性终止密码子,构建FascDNA和生物素化融合原核表达质粒PinPoint-Fas。将重组质粒转入大肠杆菌HB101,经500mmolIPTG在37℃条件下诱导4h,SDS-PAGE及Western印迹检测融合蛋白在大肠杆菌得以高效表达,表达量为细菌总蛋白的13.8%。用亲和层析树脂对生物素化融合蛋白进行亲和层析纯化,得到Fas重组的蛋白,且表达的Fas融合蛋白具有抗体结合活性。此蛋白的表达成功将解决Fas膜蛋白不易提取的难题,为深入研究Fas提供了良好材料来源 相似文献
998.
The contribution of sialic acids and of N-linked sugars to the biological activity of the receptor for IL 2 has been evaluated by treating activated cells with Neuraminidase or by growing them in the presence of inhibitors of N-linked glycosylation or processing. After treatment with Neuraminidase, Con A-activated spleen cells had not lost their ability to bind IL 2. The IL 2-absorbing capability was, however, strongly reduced after trypsinisation. 6 hours after Trypsin treatment, this property was again expressed. Proliferation of the IL 2-dependent CTLL cells was normal in the presence of Swainsonine but strongly impaired in the presence of Tunicamycin. Glycosylation of the IL 2 receptor may thus be required, but integrity of the sugars is not critical. 相似文献
999.
Jean E. Merrill 《Journal of clinical immunology》1983,3(1):42-50
Though purported to be identical cells (or in identical populations of cells), the natural killer (NK) cell mediating spontaneous natural cytotoxicity and the killer (K) cell mediating antibody-dependent cellular cytotoxicity (ADCC) may not be totally identical, at least in susceptibility to regulation by the immunomodulators prostaglandin E1 (PGE1) and interferon (IFN). We demonstrate here that NK cells are always enhanced by IFN, while K cells are inhibited from binding targets, resulting in fewer effectors at optimal concentrations of antibody. Only at 10- to 100-fold suboptimal concentrations of antibody is ADCC activity enhanced. As measured by magnitude of inhibition and dose-response titration, ADCC activity is less sensitive to the effects of PGE1 than is NK activity in the51Cr release assay and single-cell assay. After overnight incubation with or without PGE1, whatever sensitivity ADCC activity had to PGE1 is lost. However, NK cells incubated in the presence of PGE1 overnight are still sensitive to inhibition. Indomethacin boosts NK activity without having any effect on ADCC activity. Finally, NK activity is substantially reduced by overnight incubation of cells at room temperature, which has no effect on K cells. 相似文献
1000.
Comparison of radioimmunoassay and ELISA methods for detection of antibodies to chromatin components 总被引:1,自引:0,他引:1
A solid phase radioimmunoassay has been compared with an enzyme-linked immunosorbent assay (ELISA) for efficacy in measuring anti-chromatin antibodies. The low backgrounds achieved with the radioimmunoassay method produced a high signal-to-noise ratio and enabled detection of the human test antiserum at a dilution of 1:102,400. By contrast, the ELISA could detect the same antiserum only at a dilution of 1:3200 and above. The radioimmunoassay was consistently more sensitive than the ELISA for detection of anti-chromatin antibodies in a number of human and mouse sera and ascites fluid containing a monoclonal antibody. Factors affecting sensitivity in both assays are discussed. 相似文献