全文获取类型
收费全文 | 397篇 |
免费 | 26篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 7篇 |
妇产科学 | 7篇 |
基础医学 | 57篇 |
口腔科学 | 6篇 |
临床医学 | 34篇 |
内科学 | 99篇 |
皮肤病学 | 16篇 |
神经病学 | 47篇 |
特种医学 | 14篇 |
外科学 | 29篇 |
综合类 | 6篇 |
一般理论 | 1篇 |
预防医学 | 23篇 |
眼科学 | 8篇 |
药学 | 26篇 |
中国医学 | 2篇 |
肿瘤学 | 41篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 8篇 |
2020年 | 5篇 |
2019年 | 11篇 |
2018年 | 10篇 |
2017年 | 6篇 |
2016年 | 10篇 |
2015年 | 10篇 |
2014年 | 20篇 |
2013年 | 19篇 |
2012年 | 20篇 |
2011年 | 25篇 |
2010年 | 15篇 |
2009年 | 13篇 |
2008年 | 29篇 |
2007年 | 32篇 |
2006年 | 23篇 |
2005年 | 30篇 |
2004年 | 24篇 |
2003年 | 29篇 |
2002年 | 31篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1991年 | 3篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1955年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有424条查询结果,搜索用时 15 毫秒
351.
Harrison CJ Griffiths M Moorman F Schnittger S Cayuela JM Shurtleff S Gottardi E Mitterbauer G Colomer D Delabesse E Castéras V Maroc N 《Cancer Genetics and Cytogenetics》2007,173(1):17-22
Rearrangements of the MLL gene are significant in acute leukemia. Among the most frequent translocations are t(4;11)(q21;q23) and t(9;11)(p22;q23), which give rise to the MLL-AFF1 and MLL-MLLT3 fusion genes (alias MLL-AF4 and MLL-AF9) in acute lymphoblastic and acute myeloid leukemia, respectively. Current evidence suggests that determining the MLL status of acute leukemia, including precise identification of the partner gene, is important in defining appropriate treatment. This underscores the need for accurate detection methods. A novel molecular diagnostic device, the MLL FusionChip, has been successfully used to identify MLL fusion gene translocations in acute leukemia, including the precise breakpoint location. This study evaluated the performance of the MLL FusionChip within a routine clinical environment, comprising nine centers worldwide, in the analysis of 21 control and 136 patient samples. It was shown that the assay allowed accurate detection of the MLL fusion gene, regardless of the breakpoint location, and confirmed that this multiplex approach was robust in a global multicenter trial. The MLL FusionChip was shown to be superior to other detection methods. The type of molecular information provided by MLL FusionChip gave an indication of the appropriate primers to design for disease monitoring of MLL patients following treatment. 相似文献
352.
Glycoprotein G (gG) of equine herpesvirus type 1 (EHV-1), a structural component of virions and secreted from virus-infected cells, was shown to bind to a variety of different chemokines and as such might be involved in immune modulation. Little is known, however, about its role in the replication cycle and infection of EHV-1 in vivo. Here we report on the function of gG in context of virus infection in vitro and in vivo. A gG deletion mutant of pathogenic EHV-1 strain RacL11 (vL11DeltagG) was constructed and analyzed. Deletion of gG had virtually no effect on the growth properties of vL11DeltagG in cell culture when compared to parental virus or a rescuant virus vL11DeltagGR, respectively, and virus titers and plaque formation were unaffected in the absence of the glycoprotein. Similarly, in the murine model of EHV-1 infection, no significant differences in virulence between the gG deletion mutant and RacL11 or vL11DeltagGR were found at high doses of infection. However, infection of mice at lower doses revealed that the gG deletion mutant was able to replicate to higher titers in lungs of infected mice. Additionally, these mice lost significantly more weight than those infected with RacL11 and a more pronounced inflammatory response in lungs was observed. Therefore we concluded that deletion of gG in EHV-1 seems to lead to an exacerbation of respiratory disease in the mouse. 相似文献
353.
354.
Gerlinde Obermoser Scott Presnell Kelly Domico Hui Xu Yuanyuan Wang Esperanza Anguiano LuAnn Thompson-Snipes Rajaram Ranganathan Brad Zeitner Anna Bjork David Anderson Cate Speake Emily Ruchaud Jason Skinner Laia Alsina Mamta Sharma Helene Dutartre Alma Cepika Damien Chaussabel 《Immunity》2013,38(4):831-844
355.
Robert A. Colbert Monica L. DeLay Erin I. Klenk Gerlinde Layh-Schmitt 《Immunological reviews》2010,233(1):181-202
Summary: Almost four decades of research into the role of human leukocyte antigen-B27 (HLA-B27) in susceptibility to spondyloarthritis has yet to yield a convincing answer. New results from an HLA-B27 transgenic rat model now demonstrate quite convincingly that CD8+ T cells are not required for the inflammatory phenotype. Discoveries that the HLA-B27 heavy chain has a tendency to misfold during the assembly of class I complexes in the endoplasmic reticulum (ER) and to form aberrant disulfide-linked dimers after transport to the cell surface have forced the generation of new ideas about its role in disease pathogenesis. In transgenic rats, HLA-B27 misfolding generates ER stress and leads to activation of the unfolded protein response, which dramatically enhances the production of interleukin-23 (IL-23) in response to pattern recognition receptor agonists. These findings have led to the discovery of striking T-helper 17 cell activation and expansion in this animal model, consistent with results emerging from humans with spondyloarthritis and the discovery of IL23R as an additional susceptibility gene for ankylosing spondylitis. Together, these results suggest a novel link between HLA-B27 and the T-helper 17 axis through the consequences of protein misfolding and open new avenues of investigation as well as identifying new targets for therapeutic intervention in this group of diseases. 相似文献
356.
Wan-Chen Hsieh En-Yu Lai Yu-Ting Liu Yi-Fu Wang Yi-Shiuan Tzeng Lu Cui Yun-Ju Lai Hsiang-Chi Huang Jia-Hsin Huang Hung-Chih Ni Dong-Yan Tsai Jian-Jong Liang Chun-Che Liao Ya-Ting Lu Laurence Jiang Ming-Tsan Liu Jann-Tay Wang Sui-Yuan Chang Chung-Yu Chen Hsing-Chen Tsai Yao-Ming Chang Gerlinde Wernig Chia-Wei Li Kuo-I Lin Yi-Ling Lin Huai-Kuang Tsai Yen-Tsung Huang Shih-Yu Chen 《The Journal of clinical investigation》2021,131(21)
To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry–based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection. 相似文献
357.
358.
Manfred Hensel Andreas Schneeweiss Hans-Peter Sinn Gerlinde Egerer Martin Kornacker Erich Solomayer Rainer Haas Gunther Bastert Anthony D Ho 《Stem cells (Dayton, Ohio)》2002,20(1):32-40
We report on the prognostic significance of tumorbiologic parameters and CD34(+) cell dose in 120 patients with metastatic breast cancer (MBC) who received high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation as first-line treatment. Her2/neu, p53, Ki67, and bcl-2 protein expression were studied using immunohistochemical staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA-index) and tumor cell proliferation (S-phase fraction) were measured by DNA flow cytometry. The relationship between these parameters and the CD34(+) cell dose and progression free (PFS) and overall survival (OS) was analyzed. With a median follow-up period of 40 months (range, 7-89 months), no more than two metastatic sites (relative risk [RR] = 3.84 [95% confidence interval (CI) 1.49-10]; p =.005) and hyperploidy (RR = 2.58 [95% CI 1.26-5.26]; p =.009) were independent predictors of longer PFS according to multivariate analysis. Independent prognostic factors of longer OS included one or two metastatic sites (RR = 4.16 [95% CI 1.96-4.16]; p <.001), a positive combined hormone receptor status (RR = 2.45 [95% CI 1.45-4.14]; p =.001) and a high number of infused stem cells (>7.8 x 10(6) CD34(+) cells per kg body weight) (RR = 2.0 [95% CI 1.17-3.42]; p =.01). In conclusion, positive hormone receptors, < or =2 metastatic sites, high DNA-index and high CD34(+) cell dose (>7.8 x 10(6) CD34(+) cells per kg) are predictors for a favorable outcome after autotransplantation for MBC. Our observation might indicate a favorable effect of HDCT in MBC patients with overexpression of Her2/neu who might have a worse prognosis when treated with conventional chemotherapy. 相似文献
359.
Martin Waldherr Antonella Ragnini Bernhard Jank Roman Teply Gerlinde Wiesenberger Rudolf J. Schweyen 《Current genetics》1993,24(4):301-306
Disruption of the nuclear MRS2 gene (mrs2-1 mutation) causes a strong pet- phenotype in strains with mitochondrial group II introns, and a leaky pet- phenotype in strains without group II introns. MRS3 and MRS4, the genes for two mitochondrial-solute carrier proteins, can suppress both phenotypes when present in high-copy-number plasmids. In order to search for further multicopy suppressors of the mrs2-1 mutant phenotype, an yeast genomic DNA library, MW90, was constructed in YEp351 from a strain deleted for the MRS2, MRS3 and MRS4 genes. Ten different Sau3A DNA fragments that act as multicopy suppressors of the mrs2-1 respiratory-deficient phenotype were isolated from this library. Some of the newly isolated genes suppress the pet- phenotypes of mrs2-1 cells in strains with and without mitochondrial group II introns. Other genes, however, are suppressors only for the mitochondrial intron-less strains. This supports the notion that the MRS2 gene product is bifunctional i.e., it is essential for the splicing of group II introns and is also involved in processes of mitochondrial biogenesis other than RNA splicing. 相似文献
360.
Multiple-Locus Variable Number Tandem Repeat Analysis of Staphylococcus Aureus: Comparison with Pulsed-Field Gel Electrophoresis and spa-Typing
下载免费PDF全文
![点击此处可从《PLoS Clinical Trials》网站下载免费的PDF全文](/ch/ext_images/free.gif)