全文获取类型
收费全文 | 508篇 |
免费 | 21篇 |
专业分类
耳鼻咽喉 | 3篇 |
妇产科学 | 2篇 |
基础医学 | 55篇 |
口腔科学 | 1篇 |
临床医学 | 52篇 |
内科学 | 118篇 |
神经病学 | 138篇 |
特种医学 | 27篇 |
外科学 | 30篇 |
综合类 | 1篇 |
预防医学 | 61篇 |
眼科学 | 1篇 |
药学 | 7篇 |
中国医学 | 1篇 |
肿瘤学 | 32篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2021年 | 9篇 |
2020年 | 6篇 |
2019年 | 5篇 |
2018年 | 16篇 |
2017年 | 3篇 |
2016年 | 9篇 |
2015年 | 9篇 |
2014年 | 15篇 |
2013年 | 22篇 |
2012年 | 46篇 |
2011年 | 41篇 |
2010年 | 13篇 |
2009年 | 16篇 |
2008年 | 38篇 |
2007年 | 30篇 |
2006年 | 40篇 |
2005年 | 28篇 |
2004年 | 47篇 |
2003年 | 19篇 |
2002年 | 24篇 |
2001年 | 8篇 |
2000年 | 13篇 |
1999年 | 11篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1942年 | 1篇 |
1940年 | 1篇 |
排序方式: 共有529条查询结果,搜索用时 15 毫秒
1.
2.
3.
Analysis of DNA ligase IV mutations found in LIG4 syndrome patients: the impact of two linked polymorphisms 总被引:2,自引:0,他引:2
LIG4 syndrome patients have hypomorphic mutations in DNA ligase IV. Although four of the five identified patients display immunodeficiency and developmental delay, one patient was developmentally normal. The developmentally normal patient had the same homozygous mutation (R278H) in DNA ligase IV as one of the more severely affected patients, who additionally had two linked polymorphisms. Here, we examine the impact of the mutations and polymorphisms identified in the LIG4 syndrome patients. Examination of recombinant mutant proteins shows that the severity of the clinical features correlates with the level of residual ligase activity. The polymorphisms decrease the activity of DNA ligase IV by approximately 2-fold. When combined with the otherwise mild R278H mutation, the activity is reduced to a level similar to other LIG4 patients who display immunodeficiency and developmental delay. This demonstrates how coupling of a mutation and polymorphism can have a marked impact on protein function and provides an example where a polymorphism may have influenced clinical outcome. Analysis of additional mutational changes in LIG4 syndrome (R580X, R814X and G469E) have led to the identification of a nuclear localization signal in DNA ligase IV and sites impacting upon DNA ligase IV adenylation. 相似文献
4.
5.
Denis Heresbach Mehdi Alizadeh Dominique Reumaux Jean-Frdric Colombel Maryvonne Delamaire Pierre-Marie Danze Michel Gosselin Bernard Genetet Jean-Franois Bretagne Gilbert Semana 《Journal of autoimmunity》1996,9(6):777-784
The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunological markers such as atypical ANCA (p-ANCA), or to inclusion of more or less intractable UC. The aim of our study is to evaluate the interest of HLA class II and TAP genetic markers to identify different clinical forms of UC, according to p-ANCA status. Unrelated patients with a history of UC (n=91) and healthy control subjects with no personal or family history of inflammatory bowel diseases (IBD) (n=200) were included. HLA-DRB103 was less frequent in UC patients than in healthy controls (8% vs 28%,PC<0.03). No association was found with any TAP genotypes. Moreover, there was no association with the HLA-DR2 specificity, either in the entire group of UC patients (38% vs 28%) or in the p-ANCA-positive subgroup of patients (30%). The most consistent finding in the present study is that some genetic markers may characterize intractability in UC patients. HLA-DR2 was associated with poor prognosis, regardless of p-ANCA status. In HLA-DR2 and non-HLA-DR2 groups, colectomy was done in 55% and 27% of patients, respectively (PC<0.05). Furthermore, in non-HLA-DR2 patients, p-ANCA could be of interest to characterize those with more severe prognosis. Our results confirm the interest of genetic studies to define UC genetic susceptibility, taking into account intractability of the disease. They do not support the hypothesis that p-ANCA is a subclinical marker of genetic susceptibility to UC. 相似文献
6.
7.
8.
9.
Roger PM Perbost I Ticchioni M Fuzibet JG Breittmayer JP Durant J Pesce A Bernard A Dellamonica P;Groupe d'Etudes Niçois Polyvalent en Infectiologie 《The Journal of infection》2004,49(3):216-221
OBJECTIVE: Because the absence of immune restoration in HIV-infected patients efficiently treated by highly active antiretroviral therapy (HAART) may be due to excessive immune activation, we prospectively studied the effect of hydrocortisone on T-cell apoptosis in a cohort of patients with satisfactory virologic response. METHODS: Apoptosis of T-cell subsets including na?ve CD45RA(+)CD4+ T-cells was determined at baseline and at months 1 and 3 after initiation of HAART. A satisfactory immune response was defined as an increase >100/microL CD4+ T-cells at month 3 compared to baseline. RESULTS: Twenty out of 63 patients showed undetectable viral load at month 3, among whom eight exhibited a satisfactory immune response. Down-regulation spontaneous CD4+T-cell apoptosis was significant in the group of patients with a satisfactory immune response compared to the other patients. However, hydrocortisone up-regulated apoptosis of na?ve CD4+ CD45RA+ T-cells, specifically in group of patients with poor immune response, whatever the time point considered: percentage of apoptotic CD4 T-cells was 16+/-16% without hydrocortisone and 22+/-22% with hydrocortisone at month 1, and respectively, 10+/-9 and 17+/-15% at month 3 (P < 0.05) Hydrocortisone had no impact on CD8+ T-cell apoptosis, whatever the considered group. CONCLUSION: Our results suggest to not use steroid therapy as adjuvant immunotherapy in patients with less than optimal immunologic response to HAART. 相似文献
10.
HLA-B27 typing contributes to the diagnosis of ankylosing spondylitis. The classical technique of microlymphocytotoxicity
is costly and can give false-negative results. We have compared 304 samples using two relatively new methods – flow cytometry
and PCR-SSP – and evaluated their respective uses in routine analysis. Flow cytometric HLA-B27 testing was performed using
three monoclonal anti-B27 antibodies (HLA-ABC-m3, GS145.2 and FD705 clones). Cut-off values were established to differentiate HLA-B27-positive from HLA-B27-negative samples
with ROC curves. Although flow cytometric analysis with a reliable monoclonal antibody (mAb) is valuable for HLA screening,
none of the HLA-B27 flow cytometry protocols was sufficient on its own to ascertain the HLA phenotype in 100% of samples.
Two false negatives were observed with the FD705 mAb and the use of two different monoclonal antibodies did not increase the
accuracy of HLA-B27 typing. HLA-B27 typing using molecular biology is a reliable but costly technique. Therefore we suggest
that DNA typing could be used as a complementary technique and applied to samples whose HLA-B27 phenotype cannot be determined
by flow cytometry. The association of flow cytometry and DNA typing is, in our experience, an economical and reliable approach.
Received: 12 February 1998 / Accepted: 13 July 1998 相似文献