全文获取类型
收费全文 | 5533篇 |
免费 | 258篇 |
国内免费 | 24篇 |
专业分类
耳鼻咽喉 | 28篇 |
儿科学 | 120篇 |
妇产科学 | 135篇 |
基础医学 | 850篇 |
口腔科学 | 44篇 |
临床医学 | 488篇 |
内科学 | 1250篇 |
皮肤病学 | 107篇 |
神经病学 | 659篇 |
特种医学 | 203篇 |
外科学 | 581篇 |
综合类 | 28篇 |
预防医学 | 413篇 |
眼科学 | 61篇 |
药学 | 449篇 |
中国医学 | 10篇 |
肿瘤学 | 389篇 |
出版年
2023年 | 26篇 |
2022年 | 39篇 |
2021年 | 103篇 |
2020年 | 55篇 |
2019年 | 71篇 |
2018年 | 90篇 |
2017年 | 77篇 |
2016年 | 66篇 |
2015年 | 89篇 |
2014年 | 116篇 |
2013年 | 190篇 |
2012年 | 345篇 |
2011年 | 384篇 |
2010年 | 193篇 |
2009年 | 204篇 |
2008年 | 348篇 |
2007年 | 404篇 |
2006年 | 357篇 |
2005年 | 421篇 |
2004年 | 368篇 |
2003年 | 313篇 |
2002年 | 364篇 |
2001年 | 76篇 |
2000年 | 55篇 |
1999年 | 78篇 |
1998年 | 72篇 |
1997年 | 65篇 |
1996年 | 54篇 |
1995年 | 43篇 |
1994年 | 45篇 |
1993年 | 51篇 |
1992年 | 38篇 |
1991年 | 46篇 |
1990年 | 40篇 |
1989年 | 38篇 |
1988年 | 29篇 |
1987年 | 29篇 |
1986年 | 39篇 |
1985年 | 46篇 |
1984年 | 40篇 |
1983年 | 29篇 |
1982年 | 26篇 |
1981年 | 32篇 |
1980年 | 23篇 |
1979年 | 32篇 |
1978年 | 19篇 |
1976年 | 25篇 |
1975年 | 20篇 |
1974年 | 19篇 |
1973年 | 12篇 |
排序方式: 共有5815条查询结果,搜索用时 622 毫秒
51.
dit Faute MA Laurent L Ploton D Poupon MF Jardillier JC Bobichon H 《Clinical & experimental metastasis》2002,19(2):161-168
Growth of human tumor cells as three-dimensional (3D) multicellular spheroids modifies their invasive properties. Here we study the differences in the biological features of MCF-7, a human breast cancer cell line, and its multidrug resistant variant (MDR-MCF-7) cultured as spheroids or as monolayers. Three-dimensional culture decreased the proliferative rate of both cell lines, reduced the drug sensitivity of MCF-7 cells and did not affect the resistance of MDR-MCF-7 cells. Transmission electron microscopic studies and intercellular junctions labeling showed that MCF-7 spheroids had a junctional system involving E-cadherin, tight-junctions and desmosomes. In MDR-MCF-7 cell spheroids, cell cohesion was mostly due to membrane interdigitations. MDR-MCF-7 cells, but not their parental counterpart, displayed a higher invasive potential when cultured as spheroids, as shown in the Boyden chamber assay. 3D-induced invasiveness was correlated with serine protease and plasminogen activator (PA) secretion. MCF-7 cells did not show any tendency to invade, whatever the mode of culture. These results show that 3D-cultures as spheroids distinctively altered structural features of parental and MDR-MCF-7 cells. In MCF-7 cells, 3D-culture increased cell-cell contacts and drug resistance; in MDR-MCF-7 cells, it induced invasive properties. 相似文献
52.
Debril MB Renaud JP Fajas L Auwerx J 《Journal of molecular medicine (Berlin, Germany)》2001,79(1):30-47
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors, initially described as molecular targets for synthetic compounds that induce peroxisome proliferation. PPARgamma is the best characterized of the PPARs. The heterodimer of PPARgamma with the retinoid X receptor (RXR) plays a crucial role in adipogenesis and insulin sensitization. The RXR/PPARgamma heterodimer furthermore has been reported to have important immunomodulatory activities and to affect cell proliferation/differentiation pathways in various malignancies. PPARgamma is activated by a number of naturally occurring fatty acid derivatives and by several synthetic compounds, including the thiazolidinediones and L-tyrosine-based insulin sensitizers. This review gives an overview of the pleiotropic functions of PPARgamma and discusses the wide-ranging medical implications that modulation of PPARgamma activity might have for various diseases, ranging from obesity and type 2 diabetes to cancer and inflammation. 相似文献
53.
Els Robanus-Maandag Marleen Dekker Martin van der Valk Maria-Luisa Carrozza Jean-Claude Jeanny Jan-Hermen Dannenberg Anton Berns Hein te Riele 《Genes & development》1998,12(11):1599-1609
Hemizygosity for the retinoblastoma gene RB in man strongly predisposes to retinoblastoma. In the mouse, however, Rb hemizygosity leaves the retina normal, whereas in Rb−/− chimeras pRb-deficient retinoblasts undergo apoptosis. To test whether concomitant inactivation of the Rb-related gene p107 is required to unleash the oncogenic potential of pRb deficiency in the mouse retina, we inactivated both Rb and p107 by homologous recombination in embryonic stem cells and generated chimeric mice. Retinoblastomas were found in five out of seven adult pRb/p107-deficient chimeras. The retinal tumors showed amacrine cell differentiation, and therefore originated from cells committed to the inner but not the outer nuclear layer. Retinal lesions were already observed at embryonic day 17.5. At this stage, the primitive nuclear layer exhibited severe dysplasia, including rosette-like arrangements, and apoptosis. These findings provide formal proof for the role of loss of Rb in retinoblastoma development in the mouse and the first in vivo evidence that p107 can exert a tumor suppressor function. 相似文献
54.
55.
Gene transfer approaches using viruses such human adenovirus (HAdV) may provide an alternative treatment for diseases involving hematopoietic cells. Better understanding of the cellular mechanisms by which the HAdV introduces DNA into these cells should help in vector design. We examined HAdV intracellular delivery in several cell lines including B and T lymphocytes. We demonstrated that HAdV resistance in most B lymphocytes is the result of moderate HAdV uptake. In contrast, high levels of coxsackie and HAdV receptor (hCAR) are expressed on the surface of HSB2 (T cells), allowing efficient binding and uptake but no transgene expression, probably because of deficient endosomolysis and subsequent exocytose. This work demonstrates the existence of hCAR-dependent and -independent endocytic route in hematopoietic cells. Moreover, it precises the intracellular barriers to be overcome by HAdV in such cells to be infectious and gives previous information's to design new vectors for gene transfer. 相似文献
56.
Renaud Beauwens Viviane Beaujean Martin Zizi Marc Rentmeesters Jean Crabbé 《Pflügers Archiv : European journal of physiology》1986,407(6):620-624
The transepithelial flux of chloride was increased by aldosterone treatment of amphibian skin and bladder and this was reflected by increased shunt conductance. The hormonal effect depended on the presence of chloride on the epithelial side of the preparation. These changes in tissue conductance and chloride permeability appear to be a direct effect of aldosterone as they did not occur when sodium transport was stimulated with vasopressin or hypotonicity.Chloride efflux was reduced in magnitude by indacrinone and DIDS, as well as after removal of chloride from the solution on the epithelial side of the preparations. These results suggest that, rather than merely diffusing along (a) paracellular pathway(s), chloride flows through (a) cellular structure(s), notably mitochondria-rich cells. These cells can therefore be considered as targets for aldosterone.Presented in part before the Belgian Physiological Society (Beauwens et al. 1985) 相似文献
57.
Jean-Claude Brosse Maryvonne Bonnier Gilbert Legeay 《Macromolecular chemistry and physics.》1981,182(12):3457-3465
It was shown that radical polymerization of butadiene in 1-butanol and 2-butanol, initiated by hydrogen peroxide cleaved into two hydroxyl radicals by heat, leads to three types of polymers according to their respective polydispersity. It was found that the formation of these products — oligomers, polymers, and high polymers — can be influenced by modifying the experimental conditions. Thus, it is possible to obtain selectively oligomers free of polymers and polymers free of low molecular weight oligomers. 相似文献
58.
59.
Ekouevi DK Rouet F Becquet R Inwoley A Viho I Tonwe-Gold B Bequet L Dabis F Leroy V;ANRS / Ditrame Plus Study Group 《Journal of acquired immune deficiency syndromes (1999)》2004,36(2):755-757
The aim of this study performed in Abidjan, C?te d'Ivoire, was to describe the distribution of CD4+ T-cell lymphocytes (CD4) in HIV-1-infected (HIV+) pregnant women diagnosed during prenatal voluntary counseling and testing and to assess whether HIV-related immunodeficiency influenced the acceptance of an antiretroviral (ARV) package (zidovudine beginning at 36 weeks of amenorrhea plus intrapartum nevirapine) to prevent mother-to-child transmission. Between April and June 2002, a CD4 count was systematically performed in all HIV+ women (n=221) in 5 antenatal clinics carrying out voluntary counseling and testing. No difference in CD4 count was found in HIV+ women who did not return for their test result (n=50) and those who were informed of their positive serostatus (n=171) (median CD4 count: 389/mm3 vs. 420/mm3; P=0.19). We also found a lack of difference in CD4 count in those who accepted ARV (n=72) and those who did not but knew their HIV status (n=99) (median CD4 count: 405/mm3 vs. 425/mm3; P=0.47). The overall uptake of the intervention (31.9%) appeared to be independent of the maternal immune status. 相似文献
60.
Emergence of extended-spectrum-beta-lactamase (CTX-M-9)-producing multiresistant strains of Salmonella enterica serotype Virchow in poultry and humans in France 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Weill FX Lailler R Praud K Kérouanton A Fabre L Brisabois A Grimont PA Cloeckaert A 《Journal of clinical microbiology》2004,42(12):5767-5773
During 2002 to 2003, eight Salmonella enterica serotype Virchow poultry and poultry product isolates from various sources (chicken farms, poultry slaughterhouse, or retail store) and one S. enterica rough strain isolated from human feces were found to produce extended-spectrum beta-lactamase CTX-M-9. Poultry and poultry product isolates were recovered from different locations in the southwest of France. The human rough isolate had sequences of flagellin genes (fliC and fljB) typical of serotype Virchow and ribotyping and pulsed-field gel electrophoresis (PFGE) patterns closely similar to those of serotype Virchow strains. PFGE confirmed the clonal relationship between the poultry isolates, while the human isolate displayed a pattern with 94% homology. The bla(CTX-M-9) gene was located on a conjugative plasmid and was shown to be linked to orf513. Plasmid profiling found a very similar EcoRI restriction pattern in six transconjugants studied, including transconjugants obtained from the human isolate. A single hatchery, supplying chicks to the six farms, was identified. Emergence of extended-spectrum beta-lactamase-producing S. enterica strains in food animals is a major concern, as such strains could disseminate on a large scale and lead to antibiotic therapy difficulties. 相似文献