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61.
Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia 总被引:5,自引:3,他引:5
Cyclic neutropenia (CN) is a congenital hematopoietic disordercharacterized by remarkably regular oscillations of blood neutrophils from near normal to extremely low levels at 21-day intervals. Recurringepisodes of severe neutropenia lead to repetitive and sometimeslife-threatening infections. To investigate the cellular mechanism ofCN, the ultrastructure and the proliferative and survivalcharacteristics of bone marrow-derived CD34+ earlyprogenitors, CD33+/CD34 myeloid progenitors,and CD15+ neutrophil precursors from CN patients andhealthy volunteers were studied. The ultrastructural studies showedprofound apoptotic features in bone marrow progenitor cells in CN.Colony-forming assays demonstrated a 75% decrease in the number ofearly myeloid-committed colonies compared with controls. Long-termculture-initiating cell assays demonstrated a 6-fold increase inproduction of primitive progenitor cells in CN. To determine whetheraccelerated apoptosis might account for the underproduction of myeloidprogenitors, the hematopoietic subpopulations were labeled withfluorescein isothiocyanate-annexin V and analyzed by flow cytometry.Short-term culture of CN cells resulted in apoptosis of approximately65% of CD34+ cells, 80% ofCD33+/CD34 cells, and more than 70% ofCD15+ cells, as compared with 20%, 7%, and 15% apoptosisin respective control subpopulations. Evidence of accelerated apoptosisof bone marrow progenitor cells was observed in all 8 patientsparticipating in the study, regardless of the stage in the CN cycle inwhich bone marrow aspirations were obtained. Granulocytecolony-stimulating factor therapy of CN patients significantly improvedsurvival of bone marrow progenitor cells. These data indicate thatineffective production of neutrophils is due to accelerated apoptosisof bone marrow myeloid progenitor cells in CN. 相似文献
62.
Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist 总被引:2,自引:20,他引:2 下载免费PDF全文
Liles WC Broxmeyer HE Rodger E Wood B Hübel K Cooper S Hangoc G Bridger GJ Henson GW Calandra G Dale DC 《Blood》2003,102(8):2728-2730
Stromal cell-derived factor 1 (SDF1/CXCL12) and its cognate receptor, CXCR4, play key regulatory roles in CD34+ cell trafficking. We investigated whether AMD3100, a selective CXCR4 antagonist, could mobilize hematopoietic progenitor cells from marrow to peripheral blood in healthy human volunteers. Initially, 10 persons each received a single dose of AMD3100 (80 microsubcutaneously), which induced rapid, generalized leukocytosis associated with an increase in peripheral blood CD34+ cells, representing pluripotent hematopoietic progenitors by in vitro colony-forming unit assays, from 3.8 +/- 0.5/microL to 20.7 +/- 3.5/microL at 6 hours. Subsequent dose-response studies showed a maximum increase in circulating CD34+ cells from 2.6 +/- 0.3/microL to 40.4 +/- 3.4/microL at 9 hours after 240 micro/kg AMD3100. Serial administration of AMD3100 (80 microg/kg/d for 3 days) resulted in consistent, reversible increases in peripheral blood CD34+ cells. AMD3100 was well tolerated and caused only mild, transient toxicity. These findings suggest potential clinical application of AMD3100 for CD34+ cell mobilization and collection for hematopoietic stem cell transplantation. 相似文献
63.
既往研究提示白细胞介素4(IL-4)、白细胞介素4受体(IL-4RA)基因与血清总IgE水平、过敏性疾病有关。然而结论并不一致。我们的研究目的在于调查华人、马来人及印度人中IL-4、IL-4RA的3个基因位点的基因型(C590T、Ile50Val、Q576R)与血清总IgE水平是否存在相关性。 相似文献
64.
We evaluated the hematologic, rheologic, and biochemical features of erythrocytes obtained from 10 relatives of a 5-yr-old black female with hereditary pyropoikilocytosis (HPP) and severe hemolytic anemia. Erythrocyte morphology was normal in the father and five other relatives, but ghost mechanical fragility and drug-induced red cell endocytosis were increased, as was the percentage of spectrin dimers noted on 3.2% nondenaturing PAGE of spectrin extracts. Identical changes were also noted in the mother and her sister, whose erythrocytes were elliptocytic and exhibited morphological changes upon heating to 45 degrees-48 degrees C (normal 49 degrees). The two other family members were normal in every respect. SDS-PAGE analysis of membrane proteins demonstrated diminished amounts of spectrin in HPP erythrocytes, but was normal in other family members. A diffuse band (mol wt 575,000-665,000), composed entirely of spectrin, was apparent adjacent to the dimer region on nondenaturing PAGE of spectrin extracts from the propositus, mother, and aunt. In this family, HPP appears to have resulted from compound heterozygosity for two distinct genetic abnormalities (reflected by the differences between elliptocytic and nonelliptocytic carriers). Although the membrane abnormalities in carriers did not result in hemolytic anemia, they were of sufficient magnitude to allow the detection of the carrier state. 相似文献
65.
Analysis of human platelet glycoproteins IIb-IIIa and Glanzmann's thrombasthenia in whole blood by flow cytometry 总被引:4,自引:0,他引:4
Antibodies that bind to human platelet membrane glycoproteins IIb and IIIa were used to develop methods for analyzing platelet membrane components by flow cytometry. Platelets were tentatively identified by their low-intensity light scatter profiles in whole blood or platelet- rich plasma preparations. Identification of this cell population as platelets was verified by using platelet-specific antibodies and fluorescein-conjugated antiimmunoglobulin. Two-parameter analysis of light scatter versus fluorescence intensity identified greater than 98% of the cells in the "platelet" light scatter profile as platelets due to their acquired fluorescence. Both platelet-rich plasma and whole blood were used to study platelet membrane glycoproteins IIb and IIIa on a single cell basis in an unwashed system. Prostacycline was included in these preparations as a precautionary step to inhibit platelet aggregation during analysis. Flow cytometry is a successful technique for rapid detection of platelet membrane defects such as Glanzmann's thrombasthenia. Platelets from Glanzmann's thrombasthenic individuals were readily distinguished from platelets with normal levels of glycoprotein IIb and IIIa and from platelets with glycoprotein levels characteristic of heterozygote carriers of this disorder. This technique provides a sensitive tool for investigating platelet functional defects due to altered expression or deficiency of platelet surface proteins. 相似文献
66.
Programmed cell death, also known as apoptosis, is frequently initiated when cells are deprived of specific trophic factors. To investigate if accelerated apoptosis contributes to the pathogenesis of Diamond- Blackfan anemia (DBA), a rare pure red blood cell aplasia of childhood, we studied the effect of erythropoietin (epo) deprivation on erythroid progenitors and precursors from the bone marrow of DBA patients as compared with hematologically normal controls. Apoptosis in response to epo deprivation was evaluated by enumeration of colony-forming unit- erythroid (CFU-E)- and burst-forming unit-erythroid (BFU-E)-derived colonies in plasma clot semisolid culture and by the identification of typical DNA oligosomes by gel electrophoresis from marrow mononuclear cells in liquid culture. In all DBA patients there was a marked decrease in CFU-E- and BFU-E-derived colony formation compared with normal controls at comparable time points of epo deprivation, with a complete loss of CFU-E-derived colonies in semisolid culture by 9 hours of epo deprivation versus 48 hours in controls. The BFU-E-derived colony response to epo deprivation displayed a similar pattern of decrement. Apoptotic changes assessed by the presence of characteristic DNA fragmentation began in the absence of epo deprivation and were readily detected within 3 hours of epo deprivation in DBA cultures versus 9 hours in controls. We conclude that DBA is characterized by accelerated apoptosis as measured by the loss of erythroid progenitor clonogenicity and increased progenitor and precursor DNA fragmentation leading to the formation of characteristic oligosomes, consistent with an intrinsic erythroid-progenitor defect in which increased sensitivity to epo deprivation results in erythroid failure. 相似文献
67.
IDEC-C2B8 (Rituximab) Anti-CD20 Monoclonal Antibody Therapy in Patients With Relapsed Low-Grade Non-Hodgkin's Lymphoma 总被引:29,自引:14,他引:29
68.
Purpose:?In this study we assessed whether balance confidence scores changed over a 2-year follow up period, and identified predictors of balance confidence and predictors of change in balance confidence among lower limb amputees.Method:?A prospective follow-up survey of 245 community living adults with unilateral below and above knee lower limb amputation who used their prosthetic limb daily was conducted. Balance confidence, assessed using the 16-item Activity-specific Balance Confidence (ABC) Scale, socio-demographic, health and amputation related variables were collected at baseline and 2 years later.Results:?ABC scores were similar at baseline (mean?= 67.6; SD?=?25.7) and follow up (mean?=?68.0; SD?=?25.8). Lower balance confidence scores at follow up were predicted by older age, being female, use of a mobility device, poor perceived health, increased symptoms of depression, having to concentrate while walking, and fear of falling (all p?<?0.05). Predictors of change in balance confidence included gender and perceived health (all p?<?0.05).Conclusion:?Balance confidence appears to be a persistent problem in the amputee population. Health professionals are encouraged to consider balance confidence as a potentially important variable that may influence function in this clinically unique group of individuals. The identified predictor variables may be useful to clinicians in targeting individuals who require attention to improve balance confidence. 相似文献
69.
70.