全文获取类型
收费全文 | 2006篇 |
免费 | 151篇 |
国内免费 | 81篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 78篇 |
妇产科学 | 17篇 |
基础医学 | 262篇 |
口腔科学 | 27篇 |
临床医学 | 307篇 |
内科学 | 390篇 |
皮肤病学 | 34篇 |
神经病学 | 189篇 |
特种医学 | 391篇 |
外科学 | 131篇 |
综合类 | 86篇 |
预防医学 | 98篇 |
眼科学 | 9篇 |
药学 | 142篇 |
中国医学 | 1篇 |
肿瘤学 | 70篇 |
出版年
2021年 | 17篇 |
2019年 | 17篇 |
2018年 | 19篇 |
2017年 | 14篇 |
2016年 | 23篇 |
2015年 | 31篇 |
2014年 | 18篇 |
2013年 | 35篇 |
2012年 | 34篇 |
2011年 | 61篇 |
2010年 | 62篇 |
2009年 | 64篇 |
2008年 | 66篇 |
2007年 | 90篇 |
2006年 | 61篇 |
2005年 | 66篇 |
2004年 | 37篇 |
2003年 | 50篇 |
2002年 | 44篇 |
2001年 | 57篇 |
2000年 | 47篇 |
1999年 | 44篇 |
1998年 | 109篇 |
1997年 | 95篇 |
1996年 | 131篇 |
1995年 | 101篇 |
1994年 | 106篇 |
1993年 | 88篇 |
1992年 | 41篇 |
1991年 | 43篇 |
1990年 | 50篇 |
1989年 | 41篇 |
1988年 | 44篇 |
1987年 | 37篇 |
1986年 | 48篇 |
1985年 | 47篇 |
1984年 | 22篇 |
1983年 | 33篇 |
1982年 | 25篇 |
1981年 | 35篇 |
1980年 | 24篇 |
1979年 | 11篇 |
1978年 | 23篇 |
1977年 | 26篇 |
1976年 | 16篇 |
1975年 | 16篇 |
1974年 | 9篇 |
1972年 | 6篇 |
1971年 | 10篇 |
1966年 | 6篇 |
排序方式: 共有2238条查询结果,搜索用时 15 毫秒
31.
32.
Missense mutation of the erythropoietin receptor is a rare event in human erythroid malignancies 总被引:5,自引:1,他引:5
Le Couedic JP; Mitjavila MT; Villeval JL; Feger F; Gobert S; Mayeux P; Casadevall N; Vainchenker W 《Blood》1996,87(4):1502-1511
Human erythroid malignancies (polycythemia vera [PV] and erythroleukemia) are associated with erythropoietin (Epo)-independent growth and differentiation. Missense or nonsense mutations in the Epo receptor (Epo-R) have been recently described in experimental erythroleukemia in mice and in cases of erythrocytosis in humans. To search for a similar genetic alteration in erythroleukemia and PV, we entirely sequenced the exons of the Epo-R gene as well as the intron- exon junctions in these disorders using polymerase chain reaction. In 1 of 10 cases of erythroleukemia, a single allele mutation was found in the 8th Epo-R gene exon that changed asparagine 487 into a serine. No Epo-r gene mutation was found in 12 PV cases studied, but the same mutation (N487S) was found in 1 patient with polycythemia that did not fulfill the criteria of PV (polycythemia of unknown origin). We did not detect this mutation after sequencing part of the 8th exon of the Epo-R gene from 21 other patients with polycythemia of unknown origin and 51 normal controls. The Epo-R mutation was also found in Epstein-Barr virus-derived cell lines from both cases, suggesting that it is not related to the malignant clone. Therefore, this mutation does not appear to be somatic, although no familial cases were found. The biologic effect of this mutation was subsequently studied. Erythroid progenitors from the polycythemic patient normally responded to Epo, whereas those from the erythroleukemic patient were Epo-independent due to autocrine stimulation by Epo. The normal and the mutated Epo-R were transfected into the murine Ba/F3 cell line. Both types of cells displayed the same response to Epo for proliferation, differentiation, and inhibition of apoptosis. Although this mutation may destroy a consensus binding site for Grb2, no obvious differences either in the pattern of Epo-induced tyrosine phosphorylated proteins or in the binding of Grb2 to the Epo-R were observed. In conclusion, a somatic Epo-R missense mutation does not appear to be a molecular mechanism involved in the abnormal growth of human erythroleukemia and PV. However, the Epo-R mutation (N487S) that we describe is located in the same tyrosine sequence beginning at AA 485 as the one previously observed (P488S) in as case of polycythemia (Sokol et al, Exp Hematol 22:447, 1994). These results suggest that this phosphopeptide sequence may play an important role in Epo signalling. 相似文献
33.
K A Huston G G Hunder J T Lie R H Kennedy L R Elveback 《Annals of internal medicine》1978,88(2):162-167
Among the population of Olmsted County, Minnesota, 42 patients with temporal arteritis were identified during a 25-year period. The average annual incidence per 100 000 population aged 50 and older rose from 5.1 in 1950-1959 to 17.4 in 1970-1974. The prevalence of patients with a history of the diagnosis of temporal arteritis on 1 January 1975 was 133 per 100 000 population aged 50 and older. All patients received corticosteroid therapy for a range of 1 to 77 months (median, 7 months). Relapses in 10 of 11 patients were associated with corticosteroid reduction. The majority of patients recovered fully and were followed off corticosteroids for 10 months to 19 years (median, 5 years). Temporal arteritis had no significant effect on survival. Vertebral compression fractures and myopathy were the most serious complications of therapy. The presence of giant cells in biopsies was in part related to the number of sections examined, and their presence had no apparent influence on the clinical course. 相似文献
34.
Fermand JP; Chevret S; Ravaud P; Divine M; Leblond V; Dreyfus F; Mariette X; Brouet JC 《Blood》1993,82(7):2005-2009
Sixty-three patients with high tumor mass multiple myeloma were treated with high-dose chemotherapy and total body irradiation supported by autologous blood stem cell transplantation. After high-dose therapy, they were monitored for a median of 44 months. Seven patients died early from toxicity. All the other patients, including those whose disease was resistant to previous therapies, showed a tumor mass reduction. At 6 months postengraftment, 40 (71%) of the surviving patients had minimal residual disease and 11 (20%) were in apparent complete remission. During follow-up, 25 out of the 63 (39%) patients relapsed and 16 of these died; 31 (49%) had a sustained remission. The median overall and event-free survival times after transplantation were 59 and 43 months, respectively. The initial serum beta 2-microglobulin value (> or < 2.8 mg/L) and length of previous therapy (> or < 6 courses of chemotherapy) were the only significant prognostic factors. In all surviving patients, blood stem cell autograft provided satisfactory and sustained haematopoietic reconstitution most often within 15 days. High dose chemoradiotherapy followed by autologous blood stem cell transplantation is thus an important therapeutic option for young patients with aggressive multiple myeloma. 相似文献
35.
36.
37.
Detection of the chromosomal translocation t(11;14) by polymerase chain reaction in mantle cell lymphomas 总被引:7,自引:3,他引:7
Rimokh R; Berger F; Delsol G; Digonnet I; Rouault JP; Tigaud JD; Gadoux M; Coiffier B; Bryon PA; Magaud JP 《Blood》1994,83(7):1871-1875
The t(11;14)(q13;q32) and its molecular counterpart, BCL1 rearrangement, are consistent features of mantle cell lymphoma (MCL). Rearrangement is thought to deregulate the nearby CCND1 (BCL1/PRAD1) proto-oncogene, a member of the cyclin G1 gene family, and thereby to contribute to tumorigenesis. We and others have previously shown that the BCL1 locus is rearranged in 55% to 60% of MCL patients and that, on chromosome 11, more than 80% of the breakpoints are localized within a 1-kbp DNA segment known as the major translocation cluster (MTC). We have determined the nucleotide sequence for a portion of the MTC region, and constructed chromosome 11-specific oligonucleotides that were in conjunction with a consensus immunoglobulin (Ig) heavy chain joining region (JH) primer used to perform the polymerase chain reaction (PCR) to amplify t(11;14) chromosomal junctional sequences in DNA from 16 MCL patients with breakpoints in the MTC region. 15 of the 16 breakpoints that occurred at the MTC region were amenable to PCR detection. The sizes of the amplified bands, the existence or not of a Sac I site in the PCR products, and nucleotide sequencing of the amplified DNA from four patients showed that the breakpoints share a remarkable tendency to tightly cluster within 300 bp on chromosome 11, some of them occurring at the same nucleotide. On chromosome 14, the breakpoints were localized within the Ig JH. Our findings indicate that a BCL1 rearrangement can be detected using this approach in roughly one half of the MCL patients. This has implications for both the diagnosis and the clinical management of MCL. 相似文献
38.
Bernard-Soulier syndrome (BSS) platelets, which lack the membrane glycoprotein complex Ib-IX, do not adhere to subendothelium. The adhesion of platelets from two patients with BSS to subendothelial microfibrils (MFs) and type I collagen was compared in an in vitro assay adapted to patients with low platelet count. With both patients, platelet adhesion to MFs was strongly defective, whereas the adhesion to collagen was normal. The involvement of GPIb in the MFs-induced platelet adhesion was confirmed by the inhibitory effect of a MoAb (AN51) to the von Willebrand (vWF) factor binding domain of GPIb. The adhesion of platelets to MFs thus requires GPIb-IX and an axis MFs-vWF- GPIb-IX seems therefore to be prevalent in the reactivity of platelets with subendothelium. 相似文献
39.
Two kinds of erythrocytes are released in the blood of irradiated adult hybrid mice grafted with parental fetal liver cells: fetal antigen- bearing erythrocytes (Ft+ cells) and adult-type Ft- erythrocytes. Both are of parental origin, as determined by immune lysis using histocompatibility alloantigens. The latter cells make up all the recipient's red blood cells 2 mo after receipt of the graft, Ft+ cells then being no longer detected. The transient duality of erythropoiesis in irradiated adults grafted with fetal liver cells has been confirmed by studying the kinetics of CFU-E populations, as characterized by their ability to give rise to Ft+ or Ft- erythrocytes. The results are discussed in terms of environmental factors that influenc erythroid differentiation. 相似文献