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111.
Prevention of experimental colitis in SCID mice reconstituted with CD45RBhigh CD4+ T cells by blocking the CD40-CD154 interactions 总被引:4,自引:0,他引:4
Liu Z Geboes K Colpaert S Overbergh L Mathieu C Heremans H de Boer M Boon L D'Haens G Rutgeerts P Ceuppens JL 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(11):6005-6014
Increased expression of CD40 and CD40 ligand (CD40L or CD154) has been found in inflamed mucosa of human inflammatory bowel disease (IBD), and interactions between these molecules seem to be involved in local cytokine production by macrophages. However, the precise role of CD40 signaling in the pathogenesis of IBD is still poorly understood. The aim of the present study was to investigate the in vivo relevance of CD40 signaling in experimental colitis in SCID mice reconstituted with syngeneic CD45RBhighCD4+ T cells. The results demonstrated that CD40+ and CD40L+ cells as well as their mRNA levels were significantly increased in inflamed mucosa. Administration of anti-CD40L neutralizing mAb over an 8-wk period starting immediately after CD45RBhighCD4+ T cell reconstitution completely prevented symptoms of wasting disease. Intestinal mucosal inflammation was effectively prevented, as revealed by abrogated leukocyte infiltration and decreased CD54 expression and strongly diminished mRNA levels of the proinflammatory cytokines IFN-gamma, TNF, and IL-12. When colitic SCID mice were treated with anti-CD40L starting at 5 wk after T cell transfer up to 8 wk, this delayed treatment still led to significant clinical and histological improvement and down-regulated proinflammatory cytokine secretion. These data suggest that the CD40-CD40L interactions are essential for the Th1 inflammatory responses in the bowel in this experimental model of colitis. Blockade of CD40 signaling may be beneficial to human IBD. 相似文献
112.
Cross-hybridizing snake satellite, Drosophila, and mouse DNA sequences may have arisen independently 总被引:2,自引:0,他引:2
Previous reports have interpreted hybridization between snake satellite DNA
and DNA clones from a variety of distant taxonomic groups as evidence for
evolutionary conservation, which implies common ancestry (homology) and/or
convergence (analogy) to produce the cross- hybridizing sequences. We have
isolated 11 clones from a genomic library of Drosophila melanogaster, using
a cloned 2.5-kb snake satellite probe of known nucleotide sequence. We have
also analysed published sequence data from snakes, mice, and Drosophila.
These data show that (1) all of the cross-hybridization between the snake,
fly, and mouse clones can be accounted for by the presence of either of two
tandem repeats, [GATA]n and [GACA]n and (2) these tandem repeats are
organized differently among the different species. We find no evidence that
these sequences are homologous apart from the existence of the simple
repeat itself, although their divergence from a common ancestral sequence
cannot be ruled out. The sequences contain a variety of homogeneous
clusters of tandem repeats of CATA, GA, TA, and CA, as well as GATA and
GACA. We suggest that these motifs may have arisen by a self-accelerating
process involving slipped-strand mispairing of DNA. Homogeneity of the
clusters might simply be the result of a rate of accumulation of tandem
repeats that exceeds that of other mutations.
相似文献
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T lymphocytes and their CD4 subset are direct targets for the inhibitory effect of calcitriol 总被引:1,自引:0,他引:1
We studied the direct effects of the hormone calcitriol on the activation and proliferation of pure T lymphocytes and their subsets. Calcitriol inhibited the proliferation of T lymphocytes stimulated in the absence of monocytes with phytohemagglutinin (PHA) and either a monocytic culture supernatant or a combination of monocyte-derived interleukin 1 and interleukin 6. This inhibition was not influenced by the concentration of the stimulating agents. The minimal effective concentration of calcitriol was 10(-10) M. In contrast, the interleukin 2 (10 U/ml)-driven growth of PHA-stimulated T lymphocytes was not significantly altered by calcitriol at 10(-8) M. The hormone had also no influence on the T lymphocyte proliferation induced by a combination of PHA and the anti-CD28 monoclonal antibody 9.3. Pure T lymphocytes, after incubation for 5 days with PHA and monocytic factors, expressed a high level of transferrin receptors. This phenomenon was strongly suppressed on both CD4 and CD8 subsets when 10(-8) M calcitriol had been present during the culture. Moreover, the proliferation of pure CD4 cells was directly inhibited by calcitriol in similar conditions as for unseparated T lymphocytes. We conclude that T lymphocytes and their CD4 subset are direct targets for the inhibitory effect of calcitriol. 相似文献
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Asensio JL; Canada FJ; Bruix M; Gonzalez C; Khiar N; Rodriguez-Romero A; Jimenez-Barbero J 《Glycobiology》1998,8(6):569-577
The specific interaction of hevein with GlcNAc-containing oligosaccharides
has been analyzed by1H-NMR spectroscopy. The association constants for the
binding of hevein to a variety of ligands have been estimated from1H-NMR
titration experiments. The association constants increase in the order
GlcNAc-alpha(1-->6)-Man < GlcNAc < benzyl-beta-GlcNAc <
p-nitrophenyl-beta-GlcNAc < chitobiose < p-
nitrophenyl-beta-chitobioside < methyl-beta-chitobioside <
chitotriose. Entropy and enthalpy of binding for different complexes have
been obtained from van't Hoff analysis. The driving force for the binding
process is provided by a negative DeltaH0which is partially compensated by
negative DeltaS0. These negative signs indicate that hydrogen bonding and
van der Waals forces are the major interactions stabilizing the complex.
NOESY NMR experiments in water solution provided 475 accurate protein
proton-proton distance constraints after employing the MARDIGRAS program.
In addition, 15 unambiguous protein/carbohydrate NOEs were detected. All
the experimental constraints were used in a refinement protocol including
restrained molecular dynamics in order to determine the highly refined
solution conformation of this protein- carbohydrate complex. With regard to
the NMR structure of the free protein, no important changes in the protein
nOe's were observed, indicating that carbohydrate-induced conformational
changes are small. The average backbone rmsd of the 20 refined structures
was 0.055 nm, while the heavy atom rmsd was 0.116 nm. It can be deduced
that both hydrogen bonds and van der Waals contacts confer stability to the
complex. A comparison of the three-dimensional structure of hevein in
solution to those reported for wheat germ agglutinin (WGA) and hevein
itself in the solid state has also been performed. The polypeptide
conformation has also been compared to the NMR-derived structure of a
smaller antifungical peptide, Ac-AMP2.
相似文献
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