全文获取类型
收费全文 | 108篇 |
免费 | 12篇 |
出版年
2021年 | 3篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 9篇 |
2014年 | 8篇 |
2013年 | 6篇 |
2012年 | 9篇 |
2011年 | 7篇 |
2010年 | 3篇 |
2009年 | 4篇 |
2008年 | 6篇 |
2007年 | 5篇 |
2006年 | 2篇 |
2005年 | 4篇 |
2004年 | 4篇 |
2003年 | 1篇 |
2002年 | 4篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 8篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1989年 | 3篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有120条查询结果,搜索用时 31 毫秒
101.
Taferner A Micutkova L Hermann M Jansen-Dürr P Pircher H 《Journal of cell communication and signaling》2011,5(4):277-289
Insulin-like growth factor binding proteins (IGFBPs) are key regulators of insulin-like growth factor (IGF) mediated signal
transduction and thereby can profoundly influence cellular phenotypes and cell fate. Whereas IGFBPs are extracellular proteins,
intracellular activities were described for several IGFBP family members, such as IGFBP-3, which can be reinternalized by
endocytosis and reaches the nucleus through routes that remain to be fully established. Within the family of IGFBPs, IGFBP-6
is unique for its specific binding to IGF-II. IGFBP-6 was described to possess additional IGF-independent activities, which
have in part been attributed to its translocation to the nucleus; however, cellular uptake of IGFBP-6 was not described. To
further explore IGFBP-6 functions, we developed a new method for the purification of native human IGFBP-6 from cell culture
supernatants, involving a four-step affinity purification procedure, which yields highly enriched IGFBP-6. Whereas protein
purified in this way retained the capacity to interact with IGF-II and modulate IGF-dependent signal transduction, our data
suggest that, unlike IGFBP-3, human IGFBP-6 is not readily internalized by human tumor cells. To summarize, this work describes
a novel and efficient method for the purification of native human insulin-like growth factor binding protein 6 (IGFBP-6) from
human cell culture supernatants, applying a four-step chromatography procedure. Intactness of purified IGFBP-6 was confirmed
by IGF ligand Western blot and ability to modulate IGF-dependent signal transduction. Cellular uptake studies were performed
to further characterize the purified protein, showing no short-term uptake of IGFBP-6, in contrast to IGFBP-3. 相似文献
102.
Lara Bossini-Castillo Carmen P Simeon Lorenzo Beretta Jasper C Broen Madelon C Vonk Raquel Ríos-Fernández Gerard Espinosa Patricia Carreira María T Camps Maria J Castillo Miguel A González-Gay Emma Beltrán María del Carmen Freire Javier Narváez Carlos Tolosa Torsten Witte Alexander Kreuter Annemie J Schuerwegh Anna-Maria Hoffmann-Vold Roger Hesselstrand Claudio Lunardi Jacob M van Laar Meng May Chee Ariane Herrick Bobby PC Koeleman Christopher P Denton Carmen Fonseca Timothy RDJ Radstake Javier Martin 《Arthritis research & therapy》2012,14(2):1-7
Idiopathic inflammatory myopathies (IIMs) comprise a group of autoimmune diseases that are characterized by symmetrical skeletal muscle weakness and muscle inflammation with no known cause. Like other autoimmune diseases, IIMs are treated with either glucocorticoids or immunosuppressive drugs. However, many patients with an IIM are frequently resistant to immunosuppressive treatments, and there is compelling evidence to indicate that not only adaptive immune but also several non-immune mechanisms play a role in the pathogenesis of these disorders. Here, we focus on some of the evidence related to pathologic mechanisms, such as the innate immune response, endoplasmic reticulum stress, non-immune consequences of MHC class I overexpression, metabolic disturbances, and hypoxia. These mechanisms may explain how IIM-related pathologic processes can continue even in the face of immunosuppressive therapies. These data indicate that therapeutic strategies in IIMs should be directed at both immune and non-immune mechanisms of muscle damage. 相似文献
103.
104.
Effect of rabbit anti-asialo GM1 treatment in vivo or with anti-asialo GM1 plus complement in vitro on cytotoxic T cell activities 总被引:9,自引:0,他引:9
L Stitz J Baenziger H Pircher H Hengartner R M Zinkernagel 《Journal of immunology (Baltimore, Md. : 1950)》1986,136(12):4674-4680
The susceptibility of cytotoxic effector lymphocytes and their induction to in vivo or in vitro treatment with rabbit anti-neutral glycolipid ganglio-N-tetraosylceramide (anti-ASGM1) antiserum was investigated. Intravenous injection of anti-ASGM1 antiserum eliminated measurable natural killer (NK) cell activity in spleen cells of mice infected for 5 days with Vaccinia virus, or for 8 days with lymphocytic choriomeningitis virus (LCMV) if injected 24 hr prior to testing. In addition, this treatment lowered measurable virus-specific cytotoxic T cell activity by 60 to 95%. Virus-specific cytotoxic T cell and NK cell activity generated during a primary infection in vivo was also sensitive to treatment in vitro with anti-ASGM1 antiserum (1/300 to 1/600 dilution) plus rabbit complement at a dilution of 1/15 (20 to 50% cell death, more than 30-fold decrease of cytotoxic activity); in vitro treatment with rabbit complement alone often enhanced NK and cytotoxic T cell activity slightly. In vivo treatment with anti-ASGM1 before primary immunization decreased generation of primary CTL only if high doses of anti-ASGM1 antiserum were injected twice. Antiviral T cells generated during secondary stimulation in vitro and alloreactive cytotoxic T cells from a mixed lymphocyte culture were resistant to treatment in vitro with anti-ASGM1 plus complement at the end of the culture period. Treatment in vitro of in vivo-primed responder spleen cells with anti-ASGM1 plus complement before their addition to a secondary restimulation culture resulted in complete inhibition of a secondary antiviral cytotoxic T cell response. In vivo treatment with anti-ASGM1 24 hr before their spleen cells were harvested and restimulated in vitro significantly reduced the virus-specific T cell activity of mice that had been immunized with virus several weeks previously. A cloned T cell line exclusively exerting NK-like activity was resistant, and two cloned virus-specific cytotoxic T cell lines were susceptible to treatment with anti-ASGM1 plus complement in vitro. These results caution the general use of rabbit anti-ASGM1 as a marker to distinguish NK from CTL cells; they indicate a possible relationship between NK and CTL cells and suggest that in vitro culture of lymphocytes may alter or select the cell surface expression or availability of the ASGM1 marker(s). 相似文献
105.
Phylogenetic relationships among prokaryotic and eukaryotic catalases 总被引:13,自引:1,他引:12
Seventy-four catalase protein sequences, including 29 bacterial, 8 fungal,
7 animal, and 30 plant sequences, were compiled, and 70 were used for
phylogenetic reconstruction. The core of the resulting tree revealed
unique, separate groups of plant and animal catalases, two groups of fungal
catalases, and three groups of bacterial catalases. The only overlap of
kingdoms occurred within one branch and involved fungal and bacterial
large-subunit enzymes. The other fungal branch was closely linked to the
group of animal enzymes. Group I bacterial catalases were more closely
related to the plant enzymes and contained such diverse taxa as the
Gram-positive Listeria seeligeri, Deinocococcus radiodurans, and
gamma-proteobacteria. Group III bacterial sequences were more closely
related to fungal and animal sequences and included enzymes from a broad
range of bacteria including high- and low-GC Gram positives,
proteobacteria, and a bacteroides species. Group II was composed of
large-subunit catalases from diverse sources including Gram positives
(low-GC Bacilli and high-GC Mycobacteria), proteobacteria, and species of
the filamentous fungus Aspergillus. These data can be interpreted in terms
of two gene duplication events that produced a minimum of three catalase
gene family members that subsequently evolved in response to environmental
demands. Horizontal gene transfer may have been responsible for the group
II mixture of bacterial and fungal large-subunit catalases.
相似文献
106.
Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice 总被引:72,自引:0,他引:72
P S Ohashi S Oehen K Buerki H Pircher C T Ohashi B Odermatt B Malissen R M Zinkernagel H Hengartner 《Cell》1991,65(2):305-317
To address the mechanisms of tolerance to extrathymic proteins, we have generated transgenic mice expressing the lymphocytic choriomeningitis viral (LCMV) glycoprotein (GP) in the beta islet cells of the pancreas. The fate of LCMV GP-specific T cells was followed by breeding the GP transgenic mice with T cell receptor transgenic mice, specific for LCMV and H-2Db. These studies suggest that "peripheral tolerance" of self-reactive T cells does not involve clonal deletion, clonal anergy, or a decrease in the density of T cell receptors or accessory molecules. Instead, this model indicates that self-reactive cytotoxic T cells may remain functionally unresponsive, owing to a lack of appropriate T cell activation. Infection of transgenic mice with LCMV readily abolishes peripheral unresponsiveness to the self LCMV GP antigen, resulting in a CD8+ T cell-mediated diabetes. These data suggest that similar mechanisms may operate in several so-called "T cell-mediated autoimmune diseases." 相似文献
107.
Recent technical breakthroughs in generating soluble MHC class I-peptide tetramers now allow the direct visualization of virus-specific CD8 T cells after infection in vivo. However, this technique requires the knowledge of the immunodominant viral epitopes recognized by T cells. Here, we describe an alternative approach to visualize polyclonal virus-specific CD8 T cells in vivo using a simple adoptive transfer system. In our approach, C57BL/6 (Thy1.2) mice were infected with lymphocytic choriomeningitis virus, vesicular stomatitis virus, or vaccinia virus to induce virus-specific memory T cells. Tracer T cells (2 x 106) from these virus-immune mice were adoptively transferred into nonirradiated (C57BL/6 x B6.PL-Thy-1a)F1 mice. After infection of the F1-recipient mice with the appropriate virus, the transferred cells expanded vigorously, and on day 8 postinfection 60-80% of total CD8 T cells were of donor T cell origin. Under the same conditions memory CD4 T cells gave rise to at least 10 times less cell numbers than memory CD8 T cells. The transfer system described here not only allows to visualize effector and memory CD8 T cells in vivo but also to isolate them for further in vitro characterization without knowing the epitopes recognized by these Ag-specific CD8 T cells. 相似文献
108.
Background
Efficient natural transformation in Neisseria requires the presence of short DNA uptake sequences (DUSs). Doubts remain whether DUSs propagate by pure selfish molecular drive or are selected for 'safe sex' among conspecifics. 相似文献109.
Voehringer D Blaser C Grawitz AB Chisari FV Buerki K Pircher H 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(5):2415-2422
To study peripheral tolerance of CD8 T cells to a classically MHC-restricted peptide Ag expressed in hepatocytes, ALB1 transgenic (tg) mice expressing the CTL epitope GP33 of the lymphocytic choriomeningitis virus glycoprotein under control of the mouse albumin promoter were generated. ALB1 mice exclusively expressed the GP33 transgene in the liver and, at a 100- to 1000-fold lower level, in the thymus. TCR-tg mice specific for the GP33 epitope were used to directly follow GP33-specific T cells in vivo. These experiments revealed that 1) thymic expression of the GP33 transgene led to incomplete central deletion of TCR-tg cells; and 2) peripheral TCR-tg cells in ALB1 mice ignored the GP33 transgene expressed in hepatocytes. Ignorance of adoptively transferred TCR-tg cells in ALB1 mice was broken by infection with lymphocytic choriomeningitis virus, leading to induction of hepatitis in ALB1, but not in control, mice. Taken together, we have established a novel model of virus-induced CD8 T cell-mediated autoimmune hepatitis in mice and demonstrate that naive CD8 T cells may ignore Ags expressed in the liver. 相似文献
110.
Pircher TJ Geiger JN Zhang D Miller CP Gaines P Wojchowski DM 《The Journal of biological chemistry》2001,276(12):8995-9002