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51.
Therapy of severe aplastic anemia in young adults and children with allogeneic bone marrow transplantation 总被引:1,自引:1,他引:1
During an 8-year period, 28 young adults (median age 27 years) and 30 children (median age 10 years) with severe aplastic anemia have received allogeneic bone marrow transplantation (BMT) from major histocompatibility locimatched sibling donors after preparation with cyclophosphamide and total lymphoid irradiation (TLI). All recipients were previously transfused. Comparison of post-bone marrow transplantation events in adults and children reveals equivalent median time to engraftment, median duration of hospitalization, median Karnofsky assessment of activity, and equivalent low rejection rate. Although the incidence of moderate and severe acute graft-v-host disease (GVHD) and of extensive chronic GVHD was greater in adults than in children, the projected survival at 4 years of adults (67%; 95% confidence interval [CI] 49% to 85%) and of children (73%; 95% CI 57% to 89%) was equivalent. All survivors are transfusion-free and have normal peripheral blood counts. One of 28 adults and 2 of 30 children have experienced rejection, and 1 of these patients survives after a second transplant. No malignancies have been identified following transplantation. An unexpectedly high incidence of hypothyroidism has been detected and may be attributable to preparation of recipients with TLI. Therapy of severe aplastic anemia with allogeneic BMT after preparation with cyclophosphamide and TLI offers a high rate of transfusion-free survival and a low rejection rate in previously transfused young adults and children. 相似文献
52.
Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury 总被引:2,自引:0,他引:2
Redecha P Tilley R Tencati M Salmon JE Kirchhofer D Mackman N Girardi G 《Blood》2007,110(7):2423-2431
Fetal loss in patients with antiphospholipid (aPL) antibodies has been ascribed to thrombosis of placental vessels. However, we have shown that inflammation, specifically activation of complement with generation of the anaphylotoxin C5a, is an essential trigger of fetal injury. In this study, we analyzed the role of the procoagulant molecule tissue factor (TF) in a mouse model of aPL antibody-induced pregnancy loss. We found that either blockade of TF with a monoclonal antibody in wild-type mice or a genetic reduction of TF prevented aPL antibody-induced inflammation and pregnancy loss. In response to aPL antibody-generated C5a, neutrophils express TF potentiating inflammation in the deciduas and leading to miscarriages. Importantly, we showed that TF in myeloid cells but not fetal-derived cells (trophoblasts) was associated with fetal injury, suggesting that the site for pathologic TF expression is neutrophils. We found that TF expression in neutrophils contributes to respiratory burst and subsequent trophoblast injury and pregnancy loss induced by aPL antibodies. The identification of TF as an important mediator of C5a-induced oxidative burst in neutrophils in aPL-induced fetal injury provides a new target for therapy to prevent pregnancy loss in the antiphospholipid syndrome. 相似文献
53.
M Jongsma J van Unen PB van Loenen MC Michel SLM Peters AE Alewijnse 《British journal of pharmacology》2009,156(8):1305-1311
Background and purpose:
Recently, some ligands targeting the sphingosine-1-phosphate receptor subtype 3 (S1P3) have become available. The characterization of these compounds was mainly based on one functional read-out system, although S1P3 receptors are known to activate different signal transduction pathways. Therefore, this study pharmacologically characterizes these compounds using different assays.Experimental approach:
Using CHO-FlpIn cells expressing the human S1P3 receptor the potencies and maximal effects of S1P, FTY720-P, VPC23019, VPC23153 and VPC24191 were determined in three different assays [inhibition of cAMP accumulation, elevation of intracellular calcium concentrations ([Ca2+]i) and S1P3 receptor internalization].Key results:
All compounds tested inhibited forskolin-induced cAMP accumulation, increased [Ca2+]i and induced S1P3 receptor internalization but with different potencies and maximal effects. S1P was the most potent compound in all assays followed by FTY720-P. The VPC compounds were generally less potent than S1P and FTY720-P. Regarding the maximal effects, all compounds except VPC23153, behaved as full agonists in the cAMP accumulation assay. In the calcium assay, FTY720-P, VPC23019 and VPC24191 displayed partial and VPC23153 weak partial agonist activity, relative to S1P. Interestingly, treatment with the Gi inactivator Pertussis toxin, did not affect S1P-induced [Ca2+]i elevations but inhibited those in response to the other compounds, by about 50%.Conclusions and implications:
This study demonstrated differential response patterns at the S1P3 receptor for a range of ligands. These differences could indicate the presence of functional selectivity at this receptor as FTY720-P and the VPC compounds seemed to signal predominantly via Gi– whereas S1P activated Gi and Gq-coupled pathways. 相似文献54.
A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2) 总被引:13,自引:5,他引:8
Serratosa JM; Gomez-Garre P; Gallardo ME; Anta B; de Bernabe DB; Lindhout D; Augustijn PB; Tassinari CA; Malafosse RM; Topcu M; Grid D; Dravet C; Berkovic SF; de Cordoba SR 《Human molecular genetics》1999,8(2):345-352
Progressive myoclonus epilepsy of the Lafora type or Lafora disease (EPM2;
McKusick no. 254780) is an autosomal recessive disorder characterized by
epilepsy, myoclonus, progressive neurological deterioration and
glycogen-like intracellular inclusion bodies (Lafora bodies). A gene for
EPM2 previously has been mapped to chromosome 6q23- q25 using linkage
analysis and homozygosity mapping. Here we report the positional cloning of
the 6q EPM2 gene. A microdeletion within the EPM2 critical region, present
inhomozygosis in an affected individual, was found to disrupt a novel gene
encoding a putative protein tyrosine phosphatase (PTPase). The gene,
denoted EPM2, presents alternative splicing in the 5' and 3' end regions.
Mutational analysis revealed that EPM2 patients are homozygous for
loss-of-function mutations in EPM2. These findings suggest that Lafora
disease results from the mutational inactivation of a PTPase activity that
may be important in the control of glycogen metabolism.
相似文献
55.
56.
Objective: To document the pattern and sequelae of invasive pneumococcal infection in hospitalized children.
Methodology Retrospective review of Streptococcus pneumoniae (Sp) isolates from normally sterile sites from 1981 to 1992 at three paediatric centres in Sydney for demographic data, spectrum of disease, predisposing conditions, mortality, and sequelae from meningitis.
Results: Four hundred and thirty-one episodes in 417 patients were identified. Foci of infection were: meningitis, 34%; pneumonia, 29%; bacteraemia without apparent focus, 30%; and other foci, 7%. Sixty-one per cent of all cases and 64% of cases with meningitis were less than 2 years old. Predisposing conditions were present in 37%, were significantly more common in patients over age 2 years and were more common with foci other than meningitis. Overall mortality was 6.6% whereas the mortality for those with meningitis was 8%. Neurological sequelae were identified in 34% of previously normal children, and severe hearing loss occurred in 11.5%.
Conclusions The high morbidity and mortality from invasive pneumococcal infection in children justifies further evaluation of preventive strategies. 相似文献
Methodology Retrospective review of Streptococcus pneumoniae (Sp) isolates from normally sterile sites from 1981 to 1992 at three paediatric centres in Sydney for demographic data, spectrum of disease, predisposing conditions, mortality, and sequelae from meningitis.
Results: Four hundred and thirty-one episodes in 417 patients were identified. Foci of infection were: meningitis, 34%; pneumonia, 29%; bacteraemia without apparent focus, 30%; and other foci, 7%. Sixty-one per cent of all cases and 64% of cases with meningitis were less than 2 years old. Predisposing conditions were present in 37%, were significantly more common in patients over age 2 years and were more common with foci other than meningitis. Overall mortality was 6.6% whereas the mortality for those with meningitis was 8%. Neurological sequelae were identified in 34% of previously normal children, and severe hearing loss occurred in 11.5%.
Conclusions The high morbidity and mortality from invasive pneumococcal infection in children justifies further evaluation of preventive strategies. 相似文献
57.
58.
The set-up variation of 11 patients treated supine with radical radiotherapy for carcinoma of the prostate was measured with an electronic portal imaging device to determine the adequacy of set-up techniques and current margins, as well as the need for immobilization. During the treatments 172 images of the anterior fields and 159 images of the left-lateral fields were taken and the errors in treatment placement were measured by template matching. The variation in the superior-inferior direction was small, 1.4-1.6 mm (1 SD), while the medio-lateral variation was 2.8 mm (1 SD). The anterior-posterior variation was largest, 4.6 mm (1 SD) with an offset of 3.3 mm anterior. This anterior offset and large anterior-posterior variation suggests that set-up techniques were not optimal for this direction. The 1 cm margin used was adequate for set-up variation except in a small number of cases, which was mainly due to the anterior trend. Random (treatment-to-treatment) variations were small (1.1-2.3 mm; 1 SD), indicating that immobilization would result in only modest improvement in reproducibility for these supine patients. 相似文献
59.
60.