全文获取类型
收费全文 | 2766篇 |
免费 | 243篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 89篇 |
儿科学 | 202篇 |
妇产科学 | 50篇 |
基础医学 | 288篇 |
口腔科学 | 71篇 |
临床医学 | 253篇 |
内科学 | 576篇 |
皮肤病学 | 107篇 |
神经病学 | 204篇 |
特种医学 | 284篇 |
外科学 | 274篇 |
综合类 | 60篇 |
一般理论 | 2篇 |
预防医学 | 236篇 |
眼科学 | 48篇 |
药学 | 112篇 |
中国医学 | 1篇 |
肿瘤学 | 157篇 |
出版年
2022年 | 17篇 |
2021年 | 27篇 |
2019年 | 21篇 |
2018年 | 35篇 |
2017年 | 25篇 |
2016年 | 26篇 |
2015年 | 36篇 |
2014年 | 46篇 |
2013年 | 66篇 |
2012年 | 91篇 |
2011年 | 101篇 |
2010年 | 91篇 |
2009年 | 91篇 |
2008年 | 110篇 |
2007年 | 132篇 |
2006年 | 104篇 |
2005年 | 100篇 |
2004年 | 117篇 |
2003年 | 97篇 |
2002年 | 80篇 |
2001年 | 100篇 |
2000年 | 84篇 |
1999年 | 62篇 |
1998年 | 66篇 |
1997年 | 89篇 |
1996年 | 73篇 |
1995年 | 59篇 |
1994年 | 66篇 |
1993年 | 64篇 |
1992年 | 57篇 |
1991年 | 53篇 |
1990年 | 45篇 |
1989年 | 68篇 |
1988年 | 74篇 |
1987年 | 56篇 |
1986年 | 56篇 |
1985年 | 58篇 |
1984年 | 40篇 |
1983年 | 41篇 |
1982年 | 31篇 |
1981年 | 34篇 |
1980年 | 31篇 |
1979年 | 23篇 |
1978年 | 23篇 |
1977年 | 27篇 |
1976年 | 22篇 |
1975年 | 25篇 |
1974年 | 18篇 |
1970年 | 22篇 |
1965年 | 15篇 |
排序方式: 共有3014条查询结果,搜索用时 15 毫秒
61.
Although the proto-oncogene rhombotin-2 (RBTN-2) is widely expressed in most tissues, it is not expressed in T cells. We investigated the potential for overexpression of RBTN-2 to cause tumors in T cells and other tissues by constructing transgenic mice that expressed RBTN-2 under control of the metallothionein-1 promoter. Despite overexpression of RBTN-2 in all tissues, transgenic mice developed T-cell tumors only, thus indicating that tumorigenesis caused by RBTN-2 is T-cell-specific. Thymic tumors were found between 37 and 71 weeks and were invariably associated with metastasis to nonlymphoid organs. Thymuses from apparently healthy transgenic mice were also examined. In some mice there was an 10-fold increase in the CD4-CD8- thymocyte subset, yet the total number of thymocytes was the same as that in wild-type mice. Thymic homeostasis was maintained by a compensatory reduction in the CD4+CD8+ subset. The expansion of CD4-CD8- thymocytes was associated with increased expression of RBTN-2 and with increased cell proliferation. No differences were found in the proportion of thymocytes undergoing apoptosis in transgenic mice. Furthermore, RBTN-2- induced expansion of CD4-CD8- cells did not block differentiation of these cells. Thymuses with 30% CD4-CD8- cells were essentially monoclonal, indicating that all thymic immunophenotypes were derived from a single clone. Overall, our data are consistent with the following scenario: (1) RBTN-2 expression in T cells causes selective and polyclonal proliferation of CD4-CD8- thymocytes accompanied by a compensatory decrease in other thymocyte subsets; (2) a clone with growth advantage and differentiation potential is selected and populates the thymus; and (3) this clone eventually breaches homeostasis of the thymus, accompanied or followed by metastasis to other organs. 相似文献
62.
We have further characterized the biological activities, mechanism of action, and target cell populations of recombinant human and murine thrombopoietin (rhTPO and rmTPO) in in vitro human and murine model systems. Alone, hTPO or mTPO stimulated the maturation of immature murine megakaryoblasts as measured in a single cell assay. The combination of hTPO or mTPO and interleukin-6 (IL-6) resulted in a further increase in megakaryocyte differentiation in this system. Murine TPO stimulated mouse megakaryocyte progenitor development. Human megakaryocyte progenitor development was potentiated by hTPO alone and further augmented in the presence of the early-acting cytokines (IL-3) or kit ligand/stem cell factor (KL/SCF). To further define the mechanism of action of TPO, neutralization studies were performed with antisera to IL-3, granulocyte-macrophage colony-stimulating factor (GM- CSF), IL-1 beta, and IL-11. No diminution in TPO activity was observed in the presence of these antisera. Moreover, because adhesive interactions are known to modulate hematopoiesis, we studied whether hTPO might alter such interactions between human bone marrow (BM) megakaryocytes and human BM stromal fibroblasts. No changes were observed in either megakaryocyte expression of the surface molecules lymphocyte function-associated antigen-1, very late activation antigen- 4, or intercellular adhesion molecule-1 or the adhesion of megakaryocytes to stromal fibroblasts after treatment with the growth factor. Furthermore, no induction of secretion of the cytokines IL-1 alpha, IL-1 beta, GM-CSF, IL-6, granulocyte-CSF, tumor necrosis factor- alpha, transforming growth factor-beta 1, or transforming growth factor- beta 2 by primary human BM megakaryocytes was noted after treatment of the cells with hTPO. To address whether TPO affects very primitive hematopoietic progenitors, we studied the residual cells from the BMs of mice treated with high doses of 5-fluorouracil. Although no effect of mTPO alone was noted on the viability or replication of such primitive murine progenitor populations, the triple combination of IL-3 + KL/SCF + TPO stimulated growth of megakaryocyte progenitors. These results indicate that TPO is a highly lineage-specific growth factor whose primary biological effects are likely to be direct modulation of the growth and maturation of committed megakaryocyte precursors and immature megakaryoblasts. 相似文献
63.
Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia 总被引:1,自引:1,他引:1
Robinson N; Sanders JE; Benyunes MC; Beach K; Lindgren C; Thompson JA; Appelbaum FR; Fefer A 《Blood》1996,87(4):1249-1254
Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial. 相似文献
64.
Megan R. Schwarzman Janet M. Ackerman Shanaz H. Dairkee Suzanne E. Fenton Dale Johnson Kathleen M. Navarro Gwendolyn Osborne Ruthann A. Rudel Gina M. Solomon Lauren Zeise Sarah Janssen 《Environmental health perspectives》2015,123(12):1255-1264
Background
Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk.Methods
Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC.Results
The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist.Conclusions
This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor β activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.Citation
Schwarzman MR, Ackerman JM, Dairkee SH, Fenton SE, Johnson D, Navarro KM, Osborne G, Rudel RA, Solomon GM, Zeise L, Janssen S. 2015. Screening for chemical contributions to breast cancer risk: a case study for chemical safety evaluation. Environ Health Perspect 123:1255–1264; http://dx.doi.org/10.1289/ehp.1408337 相似文献65.
McGarrigle CA Mercer CH Fenton KA Copas AJ Wellings K Erens B Johnson AM 《AIDS (London, England)》2005,19(1):77-84
OBJECTIVES: To estimate the prevalence of, and identify factors associated with, HIV testing in Britain. DESIGN: A large, stratified probability sample survey of sexual attitudes and lifestyles. METHODS: A total of 12,110 16-44 year olds completed a computer-assisted face-to-face interview and self-interview. Self-reports of HIV testing, i.e. the timing, reasons for and location of testing, were included. RESULTS: A total of 32.4% of men and 31.7% of women reported ever having had an HIV test, the majority of whom were tested through blood donation. When screening for blood donation and pregnancy were excluded, 9.0% of men and 4.6% of women had had a voluntary confidential HIV test (VCT) in the past 5 years. However, one third of injecting drug users and men who have sex with men had a VCT in the past 5 years. VCT in the past 5 years was significantly associated with age, residence, ethnicity, self-perceived HIV risk, reporting greater numbers of sexual partners, new sexual partners from abroad, previous sexually transmitted infection diagnosis, and injecting non-prescribed drugs for men and women, and same-sex partners (men only). Whereas sexually transmitted disease clinics were important sites for VCT, general practice accounted for almost a quarter of VCT. CONCLUSION: HIV testing is relatively common in Britain; however, it remains largely associated with population-based blood donation and antenatal screening programmes. In contrast, VCT remains highly associated with high-risk (sexual or drug-injecting) behaviours or population sub-groups at high risk. Strategies to reduce undiagnosed prevalent HIV infection will require further normalization and wider uptake of HIV testing. 相似文献
66.
Borkowsky W Wara D Fenton T McNamara J Kang M Mofenson L McFarland E Cunningham C Duliege AM Francis D Bryson Y Burchett S Spector SA Frenkel LM Starr S Van Dyke R Jimenez E 《The Journal of infectious diseases》2000,181(3):890-896
Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented. 相似文献
67.
Clofibric acid: a potential therapeutic agent in AML and MDS 总被引:1,自引:0,他引:1
Fenton SL Drayson MT Hewison M Vickers E Brown G Bunce CM 《British journal of haematology》1999,105(2):448-451
Differentiation therapy using retinoic acids (RAs) or 1alpha25-dihydroxyvitamin D3 (D3) is an attractive alternative to chemotherapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). However, with the exception of RA therapy for acute promyelocytic leukaemia (APL), RAs and D3 are not potent enough at doses that can be tolerated by patients. We demonstrate that clofibric acid (CA) enhances the response of HL60 cells to all-trans RA and D3. Our findings and those of others in the field lead us to suggest that combination therapy using all-trans RA and CA should be considered as potential therapy for AML and MDS. 相似文献
68.
Rogstad KE Simms I Fenton KA Edwards S Fisher M Carne CA;British Cooperative Clinical Group of the British Association for Sexual Health HIV 《International journal of STD & AIDS》2005,16(5):348-352
New diagnoses of syphilis in the UK increased eight-fold between 1997 and 2002. This study, conducted in 2002, demonstrated that 31% of clinics were not confident of their expertise to obtain an adequate specimen for dark ground microscopy (DGM), and 35% were not confident of their expertise to detect treponemes on DGM. In all, 64% of clinics had observed adherence problems in HIV-positive patients treated with parenteral regimens, as against 42% with oral regimens. Also, 51% of clinics waited more than a week for the results of initial serological tests for syphilis, and 88% of clinics waited more than a week for confirmatory test results. Other concerns include the failure to perform syphilis serology consistently whenever HIV-positive patients were at risk, and the widespread use of doxycycline as a therapy for syphilis in HIV-positive patients despite concerns that this is not known to be fully treponemicidal in cerebrospinal fluid. 相似文献
69.
Deborah J. Jones Rex Forehand Jessica Cuellar Carlye Kincaid Justin Parent Nicole Fenton Nada Goodrum 《Clinical psychology review》2013,33(2):241-252
Disruptive behaviors of childhood are among the most common reasons for referral of children to mental health professionals. Behavioral parent training (BPT) is the most efficacious intervention for these problem behaviors, yet BPT is substantially underutilized beyond university research and clinic settings. With the aim of addressing this research-to-practice gap, this article highlights the considerable, but largely unrealized, potential for technology to overcome the two most pressing challenges hindering the diffusion of BPT: (1). The dearth of BPT training and supervision opportunities for therapists who work with families of children with disruptive behaviors; and (2). The failure to engage and retain families in BPT services when services are available. To this end, this review presents a theoretical framework to guide technological innovations in BPT and highlights examples of how technology is currently being harnessed to overcome these challenges. This review also discusses recommendations for using technology as a delivery vehicle to further advance the field of BPT and the potential implications of technological innovations in BPT for other areas of children's mental health are discussed. 相似文献
70.
SG Lindquist M Duno M Batbayli A Puschmann H Braendgaard S Mardosiene K Svenstrup LH Pinborg K Vestergaard LE Hjermind J Stokholm BB Andersen P Johannsen JE Nielsen 《Clinical genetics》2013,83(3):279-283
Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene. 相似文献