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AE Clarke S Bernatsky KH Costenbader MB Urowitz DD Gladman PR Fortin M Petri S Manzi DA Isenberg A Rahman D Wallace C Gordon C Peschken MA Dooley EM Ginzler C Aranow SM Edworthy O Nived S Jacobsen G Ruiz-Irastorza E Yelin SG Barr L Criswell G Sturfelt L Dreyer I Blanco L Gottesman CH Feldman R Ramsey-Goldman 《Arthritis research & therapy》2012,14(Z3):A16
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Mycobacterial lipoarabinomannan: an extraordinary lipoheteroglycan with profound physiological effects 总被引:28,自引:1,他引:27
Detailed structural and functional studies over the last decade have led to
current recognition of the mycobacterial lipoarabinomannan (LAM) as a
phosphatidylinositol anchored lipoglycan with diverse biological
activities. Fatty acylation has been demonstrated to be essential for LAM
to maintain its functional integrity although the focus has largely been on
the arabinan motifs and the terminal capping function. It has recently been
shown that the mannose caps may be involved not only in attenuating host
immune response, but also in mediating the binding of mycobacteria to and
subsequent entry into macrophages. This may further be linked to an
intracellular trafficking pathway through which LAM is thought to be
presented by CD1 to subsets of T-cells. The implication of LAM as major
histocompatibility complex (MHC)-independent T-cell epitope and the ensuing
immune response is an area of intensive studies. Another recent focus of
research is the biosynthesis of arabinan which has been shown to be
inhibitable by the anti- tuberculosis drug, ethambutol. The phenomenon of
truncated LAM as synthesized by ethambutol resistant strains provides an
invaluable handle for dissecting the array of arabinosyltransferases
involved, as well as generating much needed structural variants for further
structural and functional studies. It is hoped that with more systematic
investigations based on clinical isolates and human cell lines, the true
significance of LAM in the immunopathogenesis of tuberculosis and leprosy
can eventually be explained.
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59.
Antiviral drugs from the nucleoside analog family block volume-activated chloride channels. 总被引:2,自引:0,他引:2
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M. Gschwentner A. Susanna E. Wll M. Ritter U. O. Nagl A. Schmarda A. Laich G. M. Pinggera H. Ellemunter H. Huemer et al. 《Molecular medicine (Cambridge, Mass.)》1995,1(4):407-417
BACKGROUND: The antiviral drugs AZT and acyclovir are generally used in the treatment of infections with human immunodeficiency virus (HIV) and herpes simplex virus (HSV). These substances are known to impede virus replication by premature nucleic acid chain termination. It is not yet clear, however, if this is the sole mechanism responsible for the antiviral and/or the numerous side effects observed in patients treated with these agents. We investigated the swelling-induced chloride current in fibroblasts, which we demonstrated is closely related or identical to a cloned epithelial chloride channel, ICln: This chloride channel can be blocked by nucleotides. MATERIALS AND METHODS: Electrophysiological, fluorescence optical, and volume measurements were made to determine the effect of nucleoside analogs on the swelling-dependent chloride current (ICl) in NIH 3T3 fibroblasts and in human T cell lymphoma (H9) cells and the cAMP-dependent chloride current in CaCo cells. RESULTS: AZT and acyclovir block the swelling-dependent chloride current and the chloride flux in fibroblasts, and the regulatory volume decrease (RVD) and ICl in H9 cells. This immediate effect can be substantially reduced by the simultaneous incubation of the cells with thymidine-5'-diphosphate (TDP) or uridine, both of which are by themselves unable to affect ICl. CONCLUSIONS: We show here a novel molecular mechanism by which antiviral drugs of the nucleoside analog family could lead to impairments of the kidney, bone marrow, gastrointestinal, and neuronal functions, and how these side effects could possibly be restricted by the presence of TDP or uridine. 相似文献
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Johannes Rüdisser Erich Tasser Janette Walde Peter Huemer Kurt Lechner Alois Ortner Ulrike Tappeiner 《Journal of Insect Conservation》2017,21(4):677-688
Public participation in scientific research, now commonly referred to as citizen science, is increasingly promoted as a possibility to overcome the large-scale data limitations related to biodiversity and conservation research. Furthermore, public data-collection projects can stimulate public engagement and provide transformative learning situations. However, biodiversity monitoring depends on sound data collection and warranted data quality. Therefore, we investigated if and how trained and supervised pupils are able to systematically collect data about the occurrence of diurnal butterflies, and how this data could contribute to a permanent butterfly monitoring system. We developed a specific assessment scheme suitable for laypeople and applied it at 35 sampling sites in Tyrol, Austria. Data quality and its explanatory power to predict butterfly habitat quality was investigated comparing data collected by pupils with independent assessments of professional butterfly experts. Despite substantial identification uncertainties for some species or species groups, the data collected by pupils was successfully used to predict the general habitat quality for butterflies using a linear regression model (r²?=?0.73, p?<0.001). Applying the proposed method in a citizen science context with laypeople could support both the long term monitoring of butterfly habitat quality, as well as the efficient selection of sites for professional in-depth assessments. 相似文献