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An ATP-activated channel is involved in mitogenic stimulation of human T lymphocytes 总被引:13,自引:1,他引:13
Baricordi OR; Ferrari D; Melchiorri L; Chiozzi P; Hanau S; Chiari E; Rubini M; Di Virgilio F 《Blood》1996,87(2):682-690
We investigated the effect of pharmacologic modulation of the ATP receptor on intracellular ion changes and proliferative response of human peripheral blood lymphocytes (PBLs) and purified T lymphocytes. Extracellular ATP (ATPe) triggered in these cells an increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) and plasma membrane depolarization. Whereas both Ca2+ release from intracellular stores and influx across the plasma membrane were detected in the whole PBL population, only Ca2+ influx was observed in T cells. In the presence of near physiologic extracellular Na+ concentrations (125 mmol/L), Ca2+ permeability through the ATPe-gated channel was very low, suggesting a higher selectivity for monovalent over divalent cations. The selective P2Z agonist benzoylbenzoic ATP (BzATP) increased [Ca2+]i in the presence but not the absence of extracellular Ca2+ and also caused plasma membrane depolarization. The covalent blocker oxidized ATP (oATP), an inhibitor of P2X and P2Z receptors, prevented Ca2+ influx and plasma membrane depolarization, but had no effect on Ca2+ release from stores. Stimulation with ATPe alone had no significant effects on PBL 3H-thymidine incorporation. On the contrary, ATPe or BzATP had a synergistic effect on DNA synthesis stimulated by selective T-cell mitogens such as phytohemagglutinin, anti-CD3 monoclonal antibody, or allogenic PBLs (mixed lymphocyte cultures). Treatment with oATP inhibited mitogenic stimulation by these receptor-directed agents but not by the combined application of the Ca2+ ionophore ionomycin and phorbol myristate acetate. Interleukin-2 partially relieved inhibition by oATP. These results suggest that human T lymphocytes express a plasma membrane channel gated by ATPe that is involved in mitogenic stimulation. 相似文献
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Blood donation leads to a decrease in natural killer cell activity: a study in normal blood donors and cancer patients 总被引:2,自引:0,他引:2
Transfusion-induced immunosuppression has long been known to be beneficial for organ transplantation patients, but recent retrospective studies suggest that blood transfusions may be detrimental for patients with cancer. If autologous blood is used to avoid immunosuppression, the assumption is that the procedure, involving blood donation, is immunologically neutral. In the present study, this assumption was evaluated by monitoring 33 normal blood donors and 16 colorectal cancer patients before and after donation of 1 (500 mL) and 2 units of blood, respectively. The cancer patients belonged to the autologous arm of a randomized trial in which the effects of allogeneic versus autologous blood on cancer prognosis were studied. The patients donated 2 units of blood with an interval of 3 to 4 days between donations. Flow cytometric analysis revealed that blood donation by normal donors and cancer patients had no effect on the proportion of B, T, and natural killer (NK) cells. Only the total number of lymphocytes was significantly decreased in the normal donors on Day 12 after donation. Blood donation had no significant effect on T-cell function assessed by phytohemagglutinin stimulation in normal donors or in cancer patients donating 2 units of blood. A significant depression of NK cell function (88% and 74% of predonation levels) was observed in normal donors on Days 2 and 5 after donation; on Day 12, the activity was again normal. Colorectal cancer patients had a significantly depressed NK cell activity (54% of predonation activity) on Day 12 after the first donation.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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张军 《中医杂志(英文版)》2010,(1)
Introduction Autism is a complex developmental disability that typically appears during the first two years of man's life and is the result of a neurological disorder that affects the functioning of the brain,and the 相似文献
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Comparison of pulmonary and pleural responses of rats and hamsters to inhaled refractory ceramic fibers 总被引:1,自引:1,他引:0
Gelzleichter TR; Bermudez E; Mangum JB; Wong BA; Janszen DB; Moss OR; Everitt JI 《Toxicological sciences》1999,49(1):93-101
The present study was designed to determine whether pleural fiber burdens
or subchronic pleural fibroproliferative and inflammatory changes can help
explain the marked interspecies differences in pleural fibrosis and
mesothelioma that are observed following long-term inhalation of RCF-1
ceramic fibers by rats and hamsters. Fischer 344 rats and Syrian golden
hamsters were exposed to RCF-1 for 4 h per day, 5 days per week, for 12
consecutive weeks. Lung and pleural fiber burdens were characterized during
and after exposure. For all time points, approximately 67% of fibers
associated with lung tissues from both rats and hamsters were longer than 5
microns in length. In comparison, fibers longer than 5 microns recovered
from the pleural compartment, following a 12-week exposure and 12 weeks of
recovery, accounted for 13% (hamsters) and 4% (rats) of the distribution.
In the 12 weeks after the cessation of exposure, the number of fibers
longer than 5 microns in length remained constant in the hamster at
approximately 150 fibers per cm2 pleura. This was 2 to 3 times the
corresponding fiber surface density in the rat. Significant pulmonary and
pleural inflammation was detected at all time points and for both species.
DNA synthesis by pleural mesothelial cells was quantified by
bromodeoxyuridine uptake following 3 days of labeling. Labeling indices
were higher in hamsters than in rats, both for RCF-1-exposed and filtered
air-control animals and was highest for the parietal surface of the pleura.
Significantly greater collagen deposition was measured in the visceral
pleura of hamsters 12 weeks post-exposure but was not significantly
elevated in rats. These findings demonstrate that subchronic inhalation
exposure to RCF-1 induces pleural inflammation, mesothelial-cell turnover,
pleural fibrosis, and an accumulation of fibers with a length greater than
5 microns in the hamster. The accumulation of long fibers in the pleural
space may contribute to the pathology observed in the hamster following
chronic inhalation of RCF- 1, whereas the presence of short, thin fibers
may play a role in the acute-phase biological response seen in both
species.
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To assess the role of routine investigations in children presenting with their first febrile convulsion, the results of investigations carried out in 328 children over a 2-year period were reviewed. Lumber puncture was performed in 96% of cases and resulted in the detection of 4 cases of unsuspected meningitis, one of which was bacterial. 2 children had normal lumbar punctures on admission but developed meningococcal meningitis within 48 hours. Sugar, calcium, urea, and electrolyte estimations, and blood counts were commonly performed but were unhelpful. We suggest that lumbar puncture in those children presenting with their first febrile convulsion under the age of 18 months is the only useful routine investigation. 相似文献