全文获取类型
收费全文 | 532篇 |
免费 | 28篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 28篇 |
妇产科学 | 13篇 |
基础医学 | 93篇 |
口腔科学 | 3篇 |
临床医学 | 24篇 |
内科学 | 97篇 |
皮肤病学 | 124篇 |
神经病学 | 28篇 |
特种医学 | 19篇 |
外科学 | 47篇 |
综合类 | 1篇 |
预防医学 | 42篇 |
眼科学 | 4篇 |
药学 | 20篇 |
肿瘤学 | 14篇 |
出版年
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 9篇 |
2017年 | 8篇 |
2016年 | 7篇 |
2015年 | 2篇 |
2014年 | 8篇 |
2013年 | 16篇 |
2012年 | 23篇 |
2011年 | 29篇 |
2010年 | 15篇 |
2009年 | 11篇 |
2008年 | 15篇 |
2007年 | 20篇 |
2006年 | 27篇 |
2005年 | 34篇 |
2004年 | 30篇 |
2003年 | 23篇 |
2002年 | 18篇 |
2001年 | 23篇 |
2000年 | 16篇 |
1999年 | 19篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1996年 | 3篇 |
1995年 | 9篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 14篇 |
1991年 | 13篇 |
1990年 | 13篇 |
1989年 | 9篇 |
1988年 | 20篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 14篇 |
1984年 | 10篇 |
1983年 | 9篇 |
1982年 | 4篇 |
1980年 | 2篇 |
1979年 | 7篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1969年 | 4篇 |
1957年 | 2篇 |
排序方式: 共有562条查询结果,搜索用时 31 毫秒
1.
Four experiments were organized around a central question: What is the form of relationship between estimated stress level on the one hand and situation strain, personal resources and social support, on the other? The first experiment examined the form of the relationship between estimated level of stress, situation strain and personal resources. The participants were students. They integrated situation strain and personal resources information in a non‐additive way. In particular, the effect of personal resources on the estimated level of stress varied as a function of the level of situation strain considered. When the situation strain was low, the stress level related with this circumstance largely depended on the personal resources of the individual. When the situation strain was high, the stress level related with this circumstance was much less dependent on the personal resources of the individual. The second experiment replicated these results among first‐aid workers, fire‐fighters and persons that had recently been injured. The third and fourth experiments replicated these results in various conditions differing as regards the level of social support. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
2.
Y Magnusson G Wallukat J G Guillet A Hjalmarson J Hoebeke 《Journal of autoimmunity》1991,4(6):893-905
A synthetic peptide corresponding to the second extracellular loop of the beta 1-adrenergic receptor was used as an antigen for antibody production in three rabbits. Antibodies of high titers were obtained in all rabbits. Only one rabbit yielded antibodies which decreased radioligand binding on the receptor in a similar way to that described for autoantibodies in patients with dilated cardiomyopathy. These antibodies recognized the receptor protein in immunoblots. Epitope mapping indicated that the N-terminal sequence of the loop used as antigen was the target of the major antigen fraction. Incubation of antibodies with C6 glioma cell membranes or inner membranes of E. coli, which express the human beta 1-adrenergic receptor, resulted in a decrease in number of radioligand binding sites. This decrease was dependent on the concentration of antibody and of Mg++ ions. It was not affected by the GTP analog GppNHp or the beta 1 subtype-specific antagonist metoprolol. The agonist, isoproterenol, also induced a decrease but the effects of antibody and agonist were not additive. These results suggest that the antibodies induce a Mg(++)-dependent, 'active', labile conformation of the receptor, independent from coupling to the GTP regulatory protein, but similar to that induced by the agonist isoproterenol. This interpretation was corroborated by the beta 1-adrenergic receptor agonist-like effect of the antibodies on cardiomyocytes in culture. 相似文献
3.
4.
5.
A Avrameas J G Guillet L Chouchane A Moraillon P Sonigo A D Strosberg 《Molecular immunology》1992,29(5):565-572
The envelope protein of the feline immunodeficiency virus (FIV) was analyzed using several epitope prediction programs based on profiles of hydrophilicity, antigenicity, and probability of residues to lie on the protein surface. Tentative homologies with the immunodominant epitope sites in simian virus (SIV) or human immunodeficiency virus (HIV) such as the V3 loop, the site of cleavage between surface envelope protein (SU) and transmembrane envelope protein (TM), and sites of N-glycosylation were thus identified. Five peptides corresponding to potential epitopes were synthesized. Four out of five peptides (P99, P100, P101, P103) were from the FIV surface envelope protein (SU). The last one (P102) was from the FIV transmembrane envelope protein TM. Three of these peptides (P99, P100, and P102) were recognized in ELISA by almost all the sera from infected cats. The peptide from TM (102) was recognized by sera from both naturally infected and inoculated cats, whereas peptides P99 and P100 (from SU) were recognized mainly by sera from naturally infected cats. On the basis of these results we propose that peptides P99, and P100 from SU and P102 from TM constitute epitopes on the FIV env protein. 相似文献
6.
A mouse model of hepatocellular carcinoma: ectopic expression of fibroblast growth factor 19 in skeletal muscle of transgenic mice
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nicholes K Guillet S Tomlinson E Hillan K Wright B Frantz GD Pham TA Dillard-Telm L Tsai SP Stephan JP Stinson J Stewart T French DM 《The American journal of pathology》2002,160(6):2295-2307
Most mouse models of hepatocellular carcinoma have expressed growth factors and oncogenes under the control of a liver-specific promoter. In contrast, we describe here the formation of liver tumors in transgenic mice overexpressing human fibroblast growth factor 19 (FGF19) in skeletal muscle. FGF19 transgenic mice had elevated hepatic alpha-fetoprotein mRNA as early as 2 months of age, and hepatocellular carcinomas were evident by 10 months of age. Increased proliferation of pericentral hepatocytes was demonstrated by 5-bromo-2'-deoxyuridine incorporation in the FGF19 transgenic mice before tumor formation and in nontransgenic mice injected with recombinant FGF19 protein. Areas of small cell dysplasia were initially evident pericentrally, and dysplastic/neoplastic foci throughout the hepatic lobule were glutamine synthetase-positive, suggestive of a pericentral origin. Consistent with chronic activation of the Wingless/Wnt pathway, 44% of the hepatocellular tumors from FGF19 transgenic mice had nuclear staining for beta-catenin. Sequencing of the tumor DNA encoding beta-catenin revealed point mutations that resulted in amino acid substitutions. These findings suggest a previously unknown role for FGF19 in hepatocellular carcinomas. 相似文献
7.
Romieu R; Lacabanne V; Kayibanda M; Antoine B; Bennoun M; Chouaib S; Guillet JG; Viguier M 《International immunology》1997,9(10):1405-1413
There is now good evidence that cytokines contribute to the regulation of
tumor growth. The cytokine-driven modulation of tumor growth was
investigated during the progression of a hepatocellular carcinoma (HCC) in
SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of
liver growth correlated with increased transforming growth factor
(TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis
factor (TNF)-alpha mRNA were detected earlier during tumor development.
Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2,
IL-4 and IFN-gamma mRNA production could be reported. In vitro,
hepatocyte-like tumor cell lines established at two stages, either before
or after HCC differentiation, were characterized. The early-stage-derived
cell line produced TNF-alpha mRNA, but had barely detectable expression of
TGF-beta 1 mRNA, while later-stage- derived cell lines showed the
reciprocal pattern. All cell lines displayed a lack of sensitivity to
TNF-alpha, although some degree of sensitivity to TNF-alpha could be
observed in the presence of actinomycin-D or after treatment with
IFN-gamma. The early-stage- derived cell line was sensitive to the growth
inhibitory effects of TGF- beta 1, but late-stage-derived tumor cell lines
displayed a loss of sensitivity to TGF-beta 1 which correlated with the
increased expression of TGF-beta 1 mRNA. Altogether, this suggests that
tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression
patterns during HCC progression. This model of HCC could be of valuable
interest to assess the impact of various immunotherapeutic strategies on
modulation of tumor growth.
相似文献
8.
Production and detection of monoclonal anti-idiotype antibodies directed against a monoclonal anti-beta-adrenergic ligand antibody 总被引:2,自引:0,他引:2
A new method has been developed to raise monoclonal anti-idiotypic antibodies. Monoclonal anti-idiotypic antibodies were obtained by fusion of NS-1 myeloma cells with splenocytes of mice immunised by intravenous injections of fixed hybridoma cells bearing a monoclonal antibody specific for beta-adrenergic ligands. New screening tests were developed to analyse the resulting hybridoma supernatants for different anti-idiotypic properties. Among 23 hybridoma supernatants recognising the idiotype, 6 were found to inhibit hapten binding and 3 of these recognised beta-adrenergic receptors. 相似文献
9.
Agns Buzyn Marina Ostankovitch Anne Zerbib Mathilde Kemula Francine Connan Bruno Varet Jean-Grard Guillet Jeannine Choppin 《European journal of immunology》1997,27(8):2066-2072
Chronic myeloid leukemia (CML) is characterized cytogenetically by a t(9;22) translocation which generates a hybrid bcr-abl gene, encoding a p210bcr-abl fusion protein. The induction in vitro of leukemia-specific T cells reactive with p210bcr-abl is a strategy developed for an immunological therapeutic approach in CML. Peptides from the junction region of this chimeric protein have been considered as potential targets for a cytotoxic response against leukemic cells. However, only a few peptides encompassing the two p210bcr-abl breakpoints have been shown to bind to the most common HLA class I molecules, which limits the number of patients who could benefit from this approach. We assume that the presence of chimeric BCR-ABL protein in leukemic cells may affect processing and delivery of peptides, possibly giving rise to new epitopes at the cell surface. We selected 162 peptides from the whole sequence of this protein, including 14 peptides of the b2a2 and b3a2 junctions, which had an anchor motif for a common HLA class I molecule. We tested their ability to bind to eight HLA class I molecules (HLA-A1, -A2, -A3, -A11, -B7, -B8, -B27, -B44). We identified 48 peptides from outside the junction region, with intermediate or strong binding capacities to these HLA class I molecules contrasting with only six junction peptides with a moderate binding capacity to HLA-A3/A11, -B8, or -B44 molecules. Moreover, cytotoxic T lymphocyte lines specific for various peptides outside the junction were generated from peripheral blood mononuclear cells of HLA-A2 or -B7 healthy donors and from one CML patient. These results contribute to evaluation of immunity to the BCR-ABL chimeric protein. Further studies are required to investigate whether such epitopes are correctly processed and presented by leukemic cells. 相似文献
10.
Shankaran S Laptook AR Ehrenkranz RA Tyson JE McDonald SA Donovan EF Fanaroff AA Poole WK Wright LL Higgins RD Finer NN Carlo WA Duara S Oh W Cotten CM Stevenson DK Stoll BJ Lemons JA Guillet R Jobe AH;National Institute of Child Health Human Development Neonatal Research Network 《The New England journal of medicine》2005,353(15):1574-1584