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51.
Deeg HJ; Storb R; Thomas ED; Appelbaum F; Buckner CD; Clift RA; Doney K; Johnson L; Sanders JE; Stewart P; Sullivan KM; Witherspoon RP 《Blood》1983,61(5):954-959
Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647- 3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation. 相似文献
52.
Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression 总被引:18,自引:26,他引:18
Sullivan KM; Shulman HM; Storb R; Weiden PL; Witherspoon RP; McDonald GB; Schubert MM; Atkinson K; Thomas ED 《Blood》1981,57(2):267-276
Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD. 相似文献
53.
Inhibitory effects of interferon on mouse megakaryocytic progenitor cells in culture 总被引:3,自引:0,他引:3
Mouse bone marrow cells were grown in plasma clots, megakaryocyte formation was stimulated with human urinary erythropoietin (Ep). The expression of megakaryocyte colony forming units (CFUM) and of single megakaryocyte forming units (M) was evaluated after seven days in culture. Usually ten times more M than CFUM were found. Megakaryocytic colony formation showed a linear dependence on cell dose from 0.5 to 2 X 10(5) cells/clot. The colony size frequency distribution exhibited a single peak in the two-cell size class, followed by a continuous decrease, suggesting that cell division may occur asynchronously in cells making up a colony. Mouse L cell interferon (IF) in doses from 10 to 1000 U/ml was included in clots together with Ep. This resulted in a biphasic, dose dependent reduction of colony formation and of single megakaryocyte formation. At all doses tested CFUM were more sensitive to IF than M. These observations are best explained by a differential inhibitory effect of IF on replication of two or more classes of megakaryocytic progenitor cells. 相似文献
54.
Storb R; Prentice RL; Banaji M; Witherspoon RP; Sullivan KM; Stewart P; Sanders JE; Mason M; Doney K; Deeg J; Clift RA; Buckner CD; Appelbaum FR; Thomas ED 《Blood》1983,61(4):672-675
The present study in patients with aplastic anemia was undertaken to determine whether exposure of recipients to donor blood products 24 hr before preparation with cyclophosphamide (1) enhanced the rate of sustained engraftment of marrow from HLA-identical siblings as suggested by animal experiments, (2) increased the rejection rate, in particular in transfused patients who may already have been exposed to donor antigens by blood products, or (3) was of no relevance to the outcome of transplantation of marrow from HLA-identical siblings. One- hundred fifty-five patients were studied, of whom 78 received blood products from the marrow donor 24 hr before cyclophosphamide and 77 did not. A binary logistic regression analysis was applied to the data, simultaneously considering five previously known risk factors for rejection. Results showed that preceding transfusion of donor blood products had neither a significant beneficial nor detrimental effect on the incidence of sustained engraftment. 相似文献
55.
Clift RA; Buckner CD; Thomas ED; Bensinger WI; Bowden R; Bryant E; Deeg HJ; Doney KC; Fisher LD; Hansen JA 《Blood》1994,84(6):2036-2043
A prospective randomized study was conducted comparing two conditioning regimens for the treatment of patients with chronic myeloid leukemia in chronic phase by marrow transplantation from HLA identical siblings. Sixty-nine patients received 60 mg/kg of cyclophosphamide on each of 2 successive days followed by 6 fractions of total body irradiation each of 2.0 Gy (CY-TBI), and 73 patients received 16 mg/kg of busulfan delivered over 4 days followed by 60 mg/kg CY on each of 2 successive days (BU-CY). There was no significant difference between the CY-TBI and the BU-CY groups in the 3-year probabilities of survival (0.80 for both), relapse (0.13 for both), or event-free survival (CY-TBI, 0.68; BU-CY, 0.71) or in speed of engraftment or incidence of venocclusive disease of the liver. The 4-year probabilities of survival and event- free survival for patients transplanted within 1 year of diagnosis were 0.86 and 0.72, respectively, for each group. Significantly more patients in the CY-TBI group experienced major creatinine elevations. There was significantly more acute graft-versus-host disease in the CY- TBI group. Fever days, positive blood cultures, hospitalizations, and inpatient hospital days were significantly more common in the CY-TBI group than in the BU-CY group. In conclusion, the BU-CY regimen was better tolerated than, and associated with survival and relapse probabilities that compare favorably with, the CY-TBI regimen. 相似文献
56.
Factor VIII and factor-VIII-related antigen (FVIIIRA) were estimated in 19 patients with paraproteinaemia. The FVIIIRA levels were above the normal range in 12 cases with II of these showing an abnormal FVIII/FVIIIRA ratio. The patients could be subdivied into three groups according to their FVIIIRA levels: normal levels, levels greater than normal but less than 200%, greater than 200%. This subdivision correlated with the degree of bone involvement as assessed by radiological skeletal survey. 相似文献
57.
S ummary . Haemagglutination inhibition and immunodiffusion techniques were applied to the study of red-cell membrane protein obtained from normal human subjects, patients with hereditary spherocytosis, patients with hereditary elliptocytosis, and also from calves and monkeys.
These techniques failed to detect differences between the normal and abnormal human red cells but did show differences between the red cells of the human and the two other mammalian species. 相似文献
These techniques failed to detect differences between the normal and abnormal human red cells but did show differences between the red cells of the human and the two other mammalian species. 相似文献
58.
Fifty-seven children between the ages of 3 and 17 years with acute lymphoblastic leukemia (ALL) in chemotherapy-induced second bone marrow remission were given cyclophosphamide, total body irradiation, and bone marrow transplants from HLA-matched donors. Sixteen died of transplant- related complications. Eighteen relapsed between 56 and 833 days after transplantation, and 16 died of leukemia. Two survive in remission off treatment following chemotherapy. Twenty-three survive in continuous remission from 1.4 to 10.4 years after transplantation and the actuarial analysis shows disease-free survival of 40% with a plateau extending from 2.5 to 10.4 years. 相似文献
59.
Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases 总被引:8,自引:2,他引:8
Loss of a whole chromosome 7 or a deletion of the long arm, del(7q), are recurring abnormalities in malignant myeloid diseases. To determine the location of genes on 7q that are likely to play a role in leukemogenesis, we examined the deleted chromosome 7 homologs in a series of 81 patients with therapy-related or de novo myelodysplastic syndrome or acute myeloid leukemia. Our analysis showed that the deletions were interstitial and that there were two distinct deleted segments of 7q. The majority of patients (65 of 81 [80%]) had proximal breakpoints in bands q11-22 and distal breakpoints in q31-36; the smallest overlapping deleted segment was within q22. The remaining 16 patients had deletions involving the distal q arm with a commonly deleted segment of q32-33. To define the proximal deleted segment at 7q22 at a molecular level, we used fluorescence in situ hybridization with a panel of mapped yeast artificial chromosome (YAC) clones from 7q to examine 15 patients with deletion breakpoints in 7q22. We determined that the smallest overlapping deleted segment is contained in a well- defined YAC contig that spans 2 to 3 Mb. These studies delineate the region of 7q that must be searched to isolate a putative myeloid leukemia suppressor gene, and provide the necessary cloned DNA for more detailed physical mapping and gene isolation. 相似文献
60.
J. Schwarz J. Astermark E. D. Menius M. Carrington S. M. Donfield E. D. Gomperts G. W. Nelson J. Oldenburg A. Pavlova A. D. Shapiro C. A. Winkler E. Berntorp from the Hemophilia Inhibitor Genetics Study Combined Cohort 《Haemophilia》2013,19(1):113-118
Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in haemophilia A. It has been suggested that differences in the distribution of FVIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Data from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and inhibitor risk among individuals of genetically determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and human leucocyte antigen (HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified (N = 49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N = 223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Haplotype 3 was not an independent predictor of inhibitor risk. Furthermore, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual. 相似文献