全文获取类型
收费全文 | 145篇 |
免费 | 11篇 |
出版年
2021年 | 2篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 9篇 |
2014年 | 8篇 |
2013年 | 10篇 |
2012年 | 2篇 |
2011年 | 11篇 |
2010年 | 14篇 |
2009年 | 9篇 |
2008年 | 10篇 |
2007年 | 8篇 |
2006年 | 4篇 |
2005年 | 6篇 |
2004年 | 6篇 |
2003年 | 1篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 11篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1978年 | 1篇 |
1972年 | 1篇 |
1931年 | 1篇 |
排序方式: 共有156条查询结果,搜索用时 31 毫秒
111.
112.
113.
Plant Molecular Biology - 相似文献
114.
Stéphanie Lacotte Marion Decossas Carole Le Coz Susana Brun Sylviane Muller Hélène Dumortier 《PloS one》2013,8(3)
Humoral responses are central to the development of chronic autoimmune diseases such as systemic lupus erythematosus. Indeed, autoantibody deposition is responsible for tissue damage, the kidneys being one of the main target organs. As the source of pathogenic antibodies, plasma cells are therefore critical players in this harmful scenario, both at systemic and local levels. The aim of the present study was to analyze plasma cells in NZB/W lupus mice and to get a better understanding of the mechanisms underlying their involvement in the renal inflammation process. Using various techniques (i.e. flow cytometry, quantitative PCR, ELISpot), we identified and extensively characterized three plasma cell intermediates, according to their B220/CD138/MHCII expression levels. Each of these cell subsets displays specific proliferation and antibody secretion capacities. Moreover, we evidenced that the inflammation-related CXCR3 chemokine receptor is uniquely expressed by CD138highMHCII+ plasma cells, which encompass both short- and long-lived cells and mostly produce IgG (auto)antibodies. Expression of CXCR3 allows efficient chemotactic responsiveness of these cells to cognate chemokines, which production is up-regulated in the kidneys of diseased NZB/W mice. Finally, using fluorescence and electron microscopy, we demonstrated the presence of CD138+CXCR3+IgG+ cells in inflammatory areas in the kidneys, where they are very likely involved in the injury process. Thus, early differentiated CD138highMHCII+ rather than terminally differentiated CD138highMHCIIlow plasma cells may be involved in the renal inflammatory injury in lupus, due to CXCR3 expression and IgG secretion. 相似文献
115.
116.
117.
Robert S. Jansen Hilde Rosing Wiete Kromdijk Rob ter Heine Jan HM Schellens Jos H. Beijnen 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(7-8):621-627
Emtricitabine (FTC) and tenofovir (TFV) are widely used antiviral agents that require intracellular phosphorylation to become active. This article describes the development and validation of an assay for the simultaneous quantification of FTC mono-, di- and triphosphate (FTC-MP, -DP and -TP), TFV and TFV mono- and diphosphate (TFV-MP and -DP) in peripheral blood mononuclear cells. Reference compounds and internal standards were obtained by thermal degradation of FTC-TP, TFV-DP, stable isotope-labeled TFV-DP and stable isotope-labeled cytosine triphosphate. Cells were lysed in methanol:water (70:30, v/v) and the extracted nucleotides were analyzed using weak anion-exchange chromatography coupled with tandem mass spectrometry. Calibration ranges in PBMC lysate from 0.727 to 36.4, 1.33 to 66.4 and 1.29 to 64.6 nM for FTC-MP, FTC-DP and FTC-TP and from 1.51 to 75.6, 1.54 to 77.2 and 2.54 to 127 nM for TFV, TFV-MP and TFV-DP, respectively, were validated. Accuracies were within ?10.3 and 16.7% deviation at the lower limit of quantification at which the coefficients of variation were less than 18.2%. At the other tested levels accuracies were within ?14.3 and 9.81% deviation and the coefficients of variation lower than 14.7%. The stability of the compounds was assessed under various analytically relevant conditions. The method was successfully applied to clinical samples. 相似文献
118.
119.
Alexis Dumortier André-Dante Durham Matteo Di Piazza Sophie Vauclair Ute Koch Gisèle Ferrand Isabel Ferrero Shadmehr Demehri Lynda Li Song Andrew G. Farr Warren J. Leonard Raphael Kopan Lucio Miele Daniel Hohl Daniela Finke Freddy Radtke 《PloS one》2010,5(2)
Background
The Notch pathway is essential for proper epidermal differentiation during embryonic skin development. Moreover, skin specific loss of Notch signaling in the embryo results in skin barrier defects accompanied by a B-lymphoproliferative disease. However, much less is known about the consequences of loss of Notch signaling after birth.Methodology and Principal Findings
To study the function of Notch signaling in the skin of adult mice, we made use of a series of conditional gene targeted mice that allow inactivation of several components of the Notch signaling pathway specifically in the skin. We demonstrate that skin-specific inactivation of Notch1 and Notch2 simultaneously, or RBP-J, induces the development of a severe form of atopic dermatitis (AD), characterized by acanthosis, spongiosis and hyperkeratosis, as well as a massive dermal infiltration of eosinophils and mast cells. Likewise, patients suffering from AD, but not psoriasis or lichen planus, have a marked reduction of Notch receptor expression in the skin. Loss of Notch in keratinocytes induces the production of thymic stromal lymphopoietin (TSLP), a cytokine deeply implicated in the pathogenesis of AD. The AD-like associated inflammation is accompanied by a myeloproliferative disorder (MPD) characterized by an increase in immature myeloid populations in the bone marrow and spleen. Transplantation studies revealed that the MPD is cell non-autonomous and caused by dramatic microenvironmental alterations. Genetic studies demontrated that G-CSF mediates the MPD as well as changes in the bone marrow microenvironment leading to osteopenia.Significance
Our data demonstrate a critical role for Notch in repressing TSLP production in keratinocytes, thereby maintaining integrity of the skin and the hematopoietic system. 相似文献120.
Mohamed M Thabet Thomas WJ Huizinga Désirée M van der Heijde Annette HM van der Helm-van Mil 《Arthritis research & therapy》2009,11(5):R155