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91.
Atorvastatin induces T cell anergy via phosphorylation of ERK1 总被引:4,自引:0,他引:4
Waiczies S Prozorovski T Infante-Duarte C Hahner A Aktas O Ullrich O Zipp F 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(9):5630-5635
Modulation of T cell response is a novel property of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors. Previously we reported the benefits of atorvastatin treatment in experimental autoimmune encephalomyelitis, the murine model of the T cell-mediated autoimmune disorder multiple sclerosis, in which a blockade of the T cell cycle by atorvastatin was attributed to an accumulation of the negative regulator p27(Kip1). We show in this report that, in line with the documented role of p27(Kip1) in T cell anergy, treatment with atorvastatin results in a deficient response to a second productive stimulus in human T cells. This effect of atorvastatin was dependent on HMG-CoA reduction and required IL-10 signaling. Importantly, atorvastatin induced an early and sustained phosphorylation of ERK1, but not ERK2, which was crucial for the induction of anergy. On the basis of the therapeutic impact of HMG-CoA reductase inhibitors, the present findings should pave the way for future therapeutic concepts related to tolerance induction in neuroinflammatory disorders such as multiple sclerosis. 相似文献
92.
The oligomerization of a family of four genetically clustered human gastrointestinal mucins 总被引:1,自引:0,他引:1
Mucins are synthesized and secreted by many epithelia. They are complex
glycoproteins that offer cytoprotection. In their functional configuration,
mucins form oligomers by a biosynthetic process that is poorly understood.
A family of four human gastrointestinal mucin genes (MUC2, MUC5AC, MUC5B,
and MUC6) is clustered to chromosome 11p15.5. To study oligomerization of
these related mucins, we performed metabolic labeling experiments with
[35S]amino acids in LS174T cells, and isolated mucin precursors by specific
immunoprecipitations that were analyzed on SDS-PAGE. Each of the precursors
of MUC2, MUC5AC, MUC5B, and MUC6 formed a single species of
disulfide-linked homo-oligomer within 1 h after pulse labeling. Based on
apparent molecular masses, these oligomeric precursors were most likely
dimers. Inhibition of vesicular RER-to-Golgi transport, with brefeldin A
and CCCP, did not affect the dimerization of MUC2 precursors, localizing
dimerization to the RER. O-Glycosylation of MUC2 followed dimerization.
Inhibition of N- glycosylation by tunicamycin retarded, but did not
inhibit, dimerization, indicating that N-glycans play a role in efficient
dimerization of MUC2 precursors. Based on sequence homology, the ability of
MUC2, MUC5AC, MUC5B and MUC6 to dimerize most likely resides in their
C-terminal domains. Thus, the RER-localized dimerization of secretory
mucins likely proceeds by similar mechanisms, which is an essential step in
the formation of the human gastrointestinal mucus- gels.
相似文献
93.
PEKKA VANHALA KRISTIINA KARHU MIKKO TUOMI KATARINA BJÖRKLÖF HANNU FRITZE HASSE HYVÄRINEN JARI LISKI 《Global Change Biology》2011,17(1):538-550
Changes in soil carbon, the largest terrestrial carbon pool, are critical for the global carbon cycle, atmospheric CO2 levels and climate. Climate warming is predicted to be most pronounced in the northern regions and therefore the large soil carbon pool residing in boreal forests will be subject to larger global warming impact than soil carbon pools in the temperate or the tropical forest. A major uncertainty in current estimates of the terrestrial carbon balance is related to decomposition of soil organic matter (SOM). We hypothesized that when soils are exposed to warmer climate the structure of the ground vegetation will change much more rapidly than the dominant tree species. This change will alter the quality and amount of litter input to the soil and induce changes in microbial communities, thus possibly altering the temperature sensitivity of SOM decomposition. We transferred organic surface soil sections from the northern borders of the boreal forest zone to corresponding forest sites in the southern borders of the boreal forest zone and studied the effects of warmer climate after an adaptation period of 2 years. The results showed that initially ground vegetation and soil microbial community structure and community functions were different in northern and southern forest sites and that 2 years of exposure to warmer climate was long enough to cause changes in these ecological indicators. The rate of SOM decomposition was approximately equally sensitive to temperature irrespective of changes in vegetation or microbial communities in the studied forest sites. However, as temperature sensitivity of the decomposition increases with decreasing temperature regime, the proportional increase in the decomposition rate in northern latitudes could lead to significant carbon losses from the soils. 相似文献
94.
Abstract The palatability to common carp, Cyprinus carpio L. of three newly developed differently flavoured floating pellets made from a high proportion (40%) of brewer's spent grain (BSG) was tested using a multiple-offer feeding experiment. The addition of ‘bold’ flavours, such as vanilla or strawberry essence, may help mask the unpleasant taste of some piscicides; however, their inclusion must not compromise uptake by carp. There were no significant differences between the consumption rates of the three varieties, and all flavours were readily consumed. Therefore, it is suggested that highly flavoured pellets made with BSG have a strong potential to mask the flavour of an unpalatable toxin, and further research is now needed to test this hypothesis. 相似文献
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97.
Previous studies of the effect of carbonation on taste perception have
suggested that it may be negligible, manifesting primarily in increases in
the perceived intensity of weak salt and sour stimuli. Assuming CO2
solutions in the mouth stimulate only trigeminal nerve endings, this result
is not altogether surprising; however, there are neurophysiological data
indicating that CO2 stimulates gustatory as well as trigeminal fibers. In
that case, carbonation might alter the quality profile of a stimulus
without producing substantial changes in overall taste intensity--much as
occurs when qualitatively different taste stimuli are mixed. To address
this possibility, subjects were asked to rate the total taste intensity of
moderate concentrations of stimuli representing each of the basic tastes
and their binary combinations, with an without added carbonation. They then
subdivided total taste intensity into the proportions of sweetness,
saltiness, sourness, bitterness and 'other taste qualities' they perceived.
The addition of carbonation produced only small increases in ratings of
total taste intensity. However, rather dramatic alterations in the quality
profiles of stimuli were observed, particularly for sweet and salty tastes.
The nature of the interaction is consistent with a direct effect of
carbonation/CO2 on the gustatory system, although the possibility that at
least some of the observed effects reflect trigeminal-gustatory
interactions cannot be ruled out.
相似文献
98.
99.
100.
P Zipp 《European journal of applied physiology and occupational physiology》1975,34(4):233-248
Pulse duration modulated signals were used to stimulate the extensor muscles of the hand. From this and from the isometric tension responses the frequency response of the human motor system was obtained. From the transfer characteristics of the components of the motor system which were taken from literature the frequency response of a closed-loop circuit model could be calculated. The theoretical frequency response was compared to the observed data. With increasing loop gain the model would show the characteristics of a filter tuned to the frequency of force-tremors. 相似文献