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排序方式: 共有225条查询结果,搜索用时 15 毫秒
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93.
Linda L. Kusner Michael J. Ciesielski Alexander Marx Henry J. Kaminski Robert A. Fenstermaker 《PloS one》2014,9(7)
The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders. 相似文献
94.
Manoucher Messripour Denis Weltin Ali Rastegar Lucien Ciesielski Patrick Kopp Magali Chabert Paul Mandel 《Journal of neurochemistry》1994,62(2):502-506
Abstract: Nuclear poly(ADP-ribose) polymerase levels as well as the DNA strand break levels of whole-brain neuronal and astroglial cells were investigated. Three- and 30-month-old rats were used. Low-molecular-weight neurofilaments and glutamine synthetase served as neuronal and astroglial markers, respectively. A large increase in the poly(ADP-ribose) polymerase activity was observed in the neurons (threefold) and astrocytes (3.7-fold) derived from 30-month-old rats. Similarly, the amount of poly(ADP-ribose) polymerase, evaluated per milligram of DNA, increased ∼3.5-fold in neurons and 3.9-fold in astrocytes prepared from 30-month-old rats. Whether the increase in the poly(ADP-ribose) polymerase activity was due to an enhanced rate of DNA strand break was investigated by determining the rate of DNA unwinding. A significant increase in DNA unwinding rate was detected in the neurons (2.7-fold), although a lower increase was observed in the astroglia (1.3-fold) of aged animals. 相似文献
95.
Using various chromatographic procedures, 4-aminobutyrate : 2-oxoglutarate transaminase from rat brain has been purified 2400 times with respect to the initial brain homogenate. The purified protein, which has a specific activity of 10 mumol times min -1, x mg-1 gave a single band by acrylamide gel electrophoresis and isoelectric focusing. It has a molecular weight of 105000 +/- 5000 and an isoelectric point of 6.8. In the presence of 0.1% sodium dodecylsulphate, a single protein band is seen on polyacrylamide gel, corresponding to a molecular weight of 57000 +/- 5000. N-terminal analysis reveals two chains with the same N-terminal amino acid, thus the enzyme may be considered as a dimer consisting of two identical subunits. The pH optimum for enzyme activity is 8.5. Studies of the enzymic reaction show that the general mechanism is of the ping-pong bi-bi model. The Km for 2-oxoglutarate at saturating 4-aminobutyrate extrapolated to saturating 2-oxoglutarate concentration is 4 mM. 2-Oxoglutarate competitively inhibits the enzyme with respect to 4-aminobutyrate, with a Ki of 1.8 times 10(-4) M. The same phenomenon is seen for the reverse reaction where the Ki is 6.6 times 10(-4) M for succinic semi-aldehyde. 相似文献
96.
Since the publication of our article (Roth, Gonnet, and Dessimoz: BMC Bioinformatics 2008 9: 518), we have noticed several errors, which we correct in the following. 相似文献
97.
Ciesielski MJ Apfel L Barone TA Castro CA Weiss TC Fenstermaker RA 《Cancer immunology, immunotherapy : CII》2006,55(12):1491-1503
Survivin is a member of the inhibitor of apoptosis protein family. Gliomas and many other tumors express survivin at high levels; whereas, normal fully differentiated cells generally do not. Therefore, survivin represents a tumor-specific target for cancer vaccine therapy. It has been shown that it is possible to produce a MHC-I-restricted cellular immunologic response to survivin vaccines. To study differences in immunogenicity between murine and human survivin proteins, we vaccinated C57BL/6 mice with bone marrow dendritic cells (BMDC) transfected with expression vectors containing the murine and human survivin genes. Mice vaccinated with BMDCs expressing a truncated human survivin protein developed cytotoxic T lymphocyte to subcutaneous GL261 glioma cells and exhibited prolonged tumor-free survival compared to mice vaccinated with BMDCs transfected with vector alone (P<0.01). While mice challenged with intracerebral GL261 cells had increased survival, no cures were observed. In contrast, vaccinated mice that fully resisted subcutaneous tumor challenge were rendered resistant to intracerebral GL261 re-challenge. BMDCs transfected with the full-length human survivin molecule were significantly more effective at prolonging survival than BMDCs expressing the full-length murine survivin gene (P=0.0175). Therefore, xenogeneic differences between human and murine sequences might be exploited to develop more immunogenic tumor vaccines. 相似文献
98.
Filip Ciesielski 《Chemistry and physics of lipids》2009,161(2):77-85
We propose the use of Lee-Goldburg decoupling in high-resolution natural abundance 13C CP-MAS NMR spectroscopy to obtain J-resolved multiplets from membrane lipids, and the use of these in spectral assignment and to investigate changes in molecular and segmental dynamics within chemical shift-resolved lipid groups. Spectroscopic characteristics of hydrated DPPC bilayers are reported, including J1CH-couplings from the liquid crystalline and gel phases. The observed J1θCH values are scaled in the Lee-Goldburg experiment by a factor of approximately 3−1/2 and corrected J1CH values on the order of 150 Hz compare well with indirect measurements. The J-resolved multiplets show J1θCH-couplings from the chain region to be approximately 20% lower than couplings determined from the headgroup, with backbone values falling between the two. Sensitivity of Lee-Goldburg decoupling to molecular motions reveals changes in hydrocarbon chain and backbone segmental dynamics across the main phospholipid transition and reduction in headgroup mobility below the pre-transition. 相似文献
99.
Valentina C Sladky Katja Knapp Tamas G Szabo Vincent Z Braun Laura Bongiovanni Hilda van den Bos Diana CJ Spierings Bart Westendorp Ana Curinha Tatjana Stojakovic Hubert Scharnagl Gerald Timelthaler Kaoru Tsuchia Matthias Pinter Georg Semmler Floris Foijer Alain de Bruin Thomas Reiberger Nataliya RohrUdilova Andreas Villunger 《EMBO reports》2020,21(12)
Polyploidization frequently precedes tumorigenesis but also occurs during normal development in several tissues. Hepatocyte ploidy is controlled by the PIDDosome during development and regeneration. This multi‐protein complex is activated by supernumerary centrosomes to induce p53 and restrict proliferation of polyploid cells, otherwise prone for chromosomal instability. PIDDosome deficiency in the liver results in drastically increased polyploidy. To investigate PIDDosome‐induced p53‐activation in the pathogenesis of liver cancer, we chemically induced hepatocellular carcinoma (HCC) in mice. Strikingly, PIDDosome deficiency reduced tumor number and burden, despite the inability to activate p53 in polyploid cells. Liver tumors arise primarily from cells with low ploidy, indicating an intrinsic pro‐tumorigenic effect of PIDDosome‐mediated ploidy restriction. These data suggest that hyperpolyploidization caused by PIDDosome deficiency protects from HCC. Moreover, high tumor cell density, as a surrogate marker of low ploidy, predicts poor survival of HCC patients receiving liver transplantation. Together, we show that the PIDDosome is a potential therapeutic target to manipulate hepatocyte polyploidization for HCC prevention and that tumor cell density may serve as a novel prognostic marker for recurrence‐free survival in HCC patients. 相似文献
100.
Sonja Melman Ellen NC Schoorel Carmen Dirksen Anneke Kwee Luc Smits Froukje de Boer Madelaine Jonkers Mallory D Woiski Ben Willem J Mol Johannes PR Doornbos Harry Visser Anjoke JM Huisjes Martina M Porath Friso MC Delemarre Simone MI Kuppens Robert Aardenburg Ivo MA Van Dooren Francis PJM Vrouenraets Frans TH Lim Gunilla Kleiverda Paulien CM van der Salm Karin de Boer Marko J Sikkema Jan G Nijhuis Rosella PMG Hermens Hubertina CJ Scheepers 《Implementation science : IS》2013,8(1):1-8