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21.
Ultraviolet irradiation of blood prevents transfusion-induced sensitization and marrow graft rejection in dogs 总被引:1,自引:1,他引:0
In a canine model using DLA-identical littermate pairs, we have shown that a regimen of three transfusions of donor blood given 24, 17, and 10 days before transplant uniformly leads to marrow graft rejection, presumably due to sensitization to minor (non-DLA) histocompatibility antigens. Untransfused dogs uniformly achieve sustained engraftment. In the present study, we investigated whether the exposure of blood to ultraviolet (UV) light (220-300 nm) prior to transfusion prevented sensitization of the recipient and allowed for successful marrow engraftment. Ten dogs were each given three pretransplant transfusions from the marrow donor. Each transfusion consisted of 50 mL of whole blood exposed in vitro to UV light for a total of 1.35 J/cm2. All ten dogs achieved engraftment. In contrast, all four dogs that had received sham-exposed transfusions rejected their grafts. In vitro studies revealed that although cell viability was not affected, leukocytes contained in UV-exposed blood were unable to function as stimulator cells in mixed leukocyte cultures or as accessory cells in mitogen- stimulated cultures. These data are consistent with the hypothesis that accessory cells are involved in transfusion-induced sensitization. We conclude that in vitro exposure of blood to UV light before transfusion prevents sensitization and allows for subsequent marrow engraftment. 相似文献
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23.
C Suriu M Khayat M Weiler N Kfir C Cohen A Zinger C Aslanidis G Schmitz and TC Falik-Zaccai 《Clinical genetics》2009,75(3):230-236
Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV is a rare, autosomal recessive neurologic disorder, characterized by absence of reaction to painful stimuli, mental retardation, self- mutilating behavior, anhidrosis, and recurrent episodes of hyperthermia. Mutations in the neurotrophic tyrosine kinase receptor 1, a receptor phosphorylated by nerve growth factor, have been documented in diverse ethnic groups. We identified the same novel nonsense mutation in two unrelated families of Moroccan Jewish descent, each with two affected siblings. This possible founder mutation may trace to the rural Jewish village in southern Morocco from where both these families originated. Genetic screening for the causative mutation among 300 unrelated Moroccan Jews did not reveal carriers for the causative mutation, thus excluding high risk for CIPA in this ethnic subpopulation. 相似文献
24.
Structuring a safer donor-replacement program 总被引:1,自引:0,他引:1
BACKGROUND: Replacement donors are more likely than volunteer donors to have positive or abnormal tests for transfusion-transmissible disease. In an effort to increase the donor pool, workers sought to identify a safer replacement-donor subgroup that may be acceptable for routine donations. STUDY DESIGN AND METHODS: In a retrospective review and cohort study, the replacement-donor effect was separated from the new- donor effect. The relative effect the replacement donor has on the risk of transfusion-transmissible diseases, donor retention, and frequency of returning donations was then quantified by comparison against the effect of repeat volunteer donors. RESULTS: The replacement donor had 3.1 times the risk and 0.72 times the donor retention rate and made 0.81 times as many returning donations as the repeat volunteer donor. The figures for the new-donor effect were similar. The two risks were additive, making a new replacement donor particularly hazardous. If replacement donations only from repeat replacement donors were considered, the donor risk and the number of donations per returning donor were made comparable to those for the general (combined) volunteer donor. CONCLUSION: The negative effect of the replacement donor is similar in magnitude to that of the new volunteer donor. A replacement-donation program targeting repeat replacement donors has an acceptable risk profile and may be a valuable adjunct to the collection of blood from general volunteer donors. 相似文献
25.
26.
Kaplan LD; Shiramizu B; Herndier B; Hahn J; Meeker TC; Ng V; Volberding PA; McGrath MS 《Blood》1995,85(7):1727-1735
27.
Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells 总被引:4,自引:0,他引:4
Berman E; Duigou-Osterndorf R; Krown SE; Fanucchi MP; Chou J; Hirsch MS; Clarkson BD; Chou TC 《Blood》1989,74(4):1281-1286
Azidothymidine (AZT) and interferon alpha (IFN-alpha) are among the drugs showing strong in vitro activity against the human immunodeficiency virus type-1 (HIV-1). Each drug, however, has significant toxicity against normal marrow progenitor cells that frequently proves dose-limiting in patients. In this study, AZT and recombinant IFN-alpha 2a (rIFN-alpha 2a) were tested as single agents and in combination against normal myeloid (CFU-GM) and erythroid (BFU- E) colony forming cells in a standard methylcellulose culture assay. The data were analyzed using a quantitative computerized analysis based on the median-effect principle and the isobologram equation as described by Chou and Talalay (Adv Enz Regul 22:27, 1984). The ED90 for BFU-E and CFU-GM inhibition was then compared with previously measured in vivo plasma levels of each drug and the ED90 for the anti-HIV-1 effect in vitro. We demonstrate that (a) the drugs are strongly synergistic in inhibiting marrow progenitor cell growth and that this synergism occurs at drug levels that are within the range of measured plasma levels in phase I clinical trials, (b) BFU-E are more sensitive than CFU-GM to the inhibiting effects of AZT, rIFN-alpha 2a or both drugs in combination, (c) the drug concentrations in combination that synergistically inhibit bone marrow progenitors are much higher than those required to inhibit HIV-1 replication in vitro, and (d) the anti- HIV-1 effect for the combination of AZT and rIFN-alpha 2a was clearly superior to the effect of AZT or rIFN-alpha 2a alone as indicated by the combination index and the dose-reduction index. These data suggest that substantially lower doses of AZT and rIFN-alpha than those currently being tested in clinical trials might not only maintain a strong synergistic anti-HIV-1 effect but might also avoid significant hematologic toxicity. 相似文献
28.
The effect of a zinc metalloprotease from Serratia marcescens on platelet surface glycoproteins (GP) Ib and V was analyzed. Increasing protease treatments caused progressive loss of GP Ib with appearance of the major fragment, glycocalicin, in the supernatant solution. No GP V was detected in the supernatant solution, and protease-pretreated platelets had the same capacity as control platelets to release fragment 1 of GP V in response to thrombin. The Serratia protease- pretreated platelets did show the lag before thrombin-induced dense granule secretion, characteristic of platelets modified by pretreatment with other nonstimulating proteases. Treatment with Serratia protease gives the only demonstrated selective loss of GP Ib without apparent effect on GP V. It suggests that GP V (1) does not depend on GP Ib for its association with platelets and (2) is not the substrate for protease modification of platelet function. 相似文献
29.
Purification and properties of heparin-releasable lipoprotein- associated coagulation inhibitor 总被引:6,自引:0,他引:6
The lipoprotein-associated coagulation inhibitor (LACI) is present in vivo in at least three different pools: sequestered in platelets, associated with plasma lipoproteins, and released into plasma by intravenous heparin, possibly from vascular endothelium. In this study we have purified the heparin-relesable form of LACI from post-heparin plasma and show that it is structurally different from lipoprotein LACI. The purification scheme uses heparin-agarose chromatography, immunoaffinity chromatography, and size-exclusion chromatography and results in a 185,000-fold purification with a 33% yield. Heparin- releasable LACI (HRL), as analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis, under reducing conditions, appears as a major band at 40 Kd and a minor band at 36 Kd. Immunoblot analysis suggests that the 36-Kd band arises from carboxyl-terminus proteolysis that occurs during the purification. HRL has a specific activity similar to that of HepG2 or lipoprotein LACI. HRL and lipoprotein LACI combine with lipoproteins in vitro while purified HepG2 LACI does not. I125-labeled HRL, injected into a rabbit, is cleared more slowly than I125-labeled HepG2 LACI, which may be due to attachment to lipoproteins in vivo. Preliminary evidence suggests that HRL is associated with vascular endothelium, possibly by attachment to glycosaminoglycans. 相似文献
30.
We have identified and characterized the lymphohematopoietic progenitors in the bone marrow of normal mice using a single-step methylcellulose culture assay. Lineage-negative Ly-6A/E (Sca-1)+ progenitors isolated from normal mice were plated in methylcellulose culture containing steel factor (SF), interleukin-7 (IL-7), erythropoietin (Ep), and IL-11. After 16 to 17 days of culture, pre-B- cell-containing multilineage myeloid colonies can be microscopically identified; however, flow-cytometric analysis of individual colonies for B220-positive cells proved superior to in situ microscopic identification of lymphomyeloid colonies. Approximately 10% (6/66) of the mixed colonies without a conspicuous B-cell component had B220- positive cells. The single cell origin of the lymphomyeloid colonies was confirmed by micromanipulation. Although the combination of SF, IL- 7, and Ep was sufficient to support formation of lymphomyeloid colonies, addition of IL-11, granulocyte colony-stimulating factor or IL-12 to the combination of SF, IL-7, and Ep increased the number of lymphomyeloid colonies. IL-1 alpha and IL-3 independently inhibited the expression of the B-lymphoid lineage when added to the combination of SF, IL-7, Ep, and IL-11. Approximately four times more lymphohematopoietic progenitors are present in normal mice than in mice treated with 5-fluorouracil. 相似文献