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71.
72.
Ott PA Dittrich MT Herzog BA Guerkov R Gottlieb PA Putnam AL Durinovic-Bello I Boehm BO Tary-Lehmann M Lehmann PV 《Journal of clinical immunology》2004,24(4):327-339
Human type 1 diabetes is thought to be mediated by autoreactive T cells specific for antigens expressed by pancreatic beta cells. However, it is unclear which autoantigens and determinants thereof are the targets of the autoimmune attack. Using comprehensive peptide libraries that cover the entire sequence of two major candidate autoantigens, GAD65 and proinsulin, we measured the in vivo frequencies of peptide-specific, IFN-gamma-producing memory T cells in 27 diabetic patients, 14 high risk individuals, and 15 partially HLA-matched healthy controls. Compared to the controls, both a higher number of determinants on the islet cell antigens were recognized and the frequencies of peptide specific cells were increased in patients and high risk individuals. Inclusion of signal enhancing anti-CD28 antibody further accentuated this difference. Considerable heterogeneity in peptide recognition was seen even in DRB1*04, DQB1*0302 matched individuals. Unlike its peptides, the GAD protein antigen did not recall a T cell memory response. The highly heterogeneous recognition of a multitude of peptide determinants on both autoantigens, occurring in the absence of protein recognition, and the low functional avidity of the memory cells involved jointly suggest that the autoimmune T cell repertoire in human type 1 diabetes primarily targets cryptic determinants engaged by determinant spreading. 相似文献
73.
CXCR4-transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells 总被引:4,自引:0,他引:4
Brenner S Whiting-Theobald N Kawai T Linton GF Rudikoff AG Choi U Ryser MF Murphy PM Sechler JM Malech HL 《Stem cells (Dayton, Ohio)》2004,22(7):1128-1133
Hematopoietic stem cells (HSCs) lose marrow reconstitution potential during ex vivo culture. HSC migration to stromal cell-derived factor (SDF)-1 (CXCL12) correlates with CXC chemokine receptor 4 (CXCR4) expression and marrow engraftment. We demonstrate that mobilized human CD34+ peripheral blood stem cells (CD34+ PBSCs) lose CXCR4 expression during prolonged culture. We transduced CD34+ PBSCs with retrovirus vector encoding human CXCR4 and achieved 18-fold more CXCR4 expression in over 87% of CD34+ cells. CXCR4-transduced cells yielded increased calcium flux and up to a 10-fold increase in migration to SDF-1. Six-day cultured CXCR4-transduced cells demonstrated significant engraftment in nonobese diabetic/severe combined immunodeficient mice under conditions in which control transduced cells resulted in low or no engraftment. We conclude that transduction-mediated overexpression of CXCR4 significantly improves marrow engraftment of cultured PBSCs. 相似文献
74.
Honl M Rentzsch R Schwieger K Carrero V Dierk O Dries S Louis H Pude F Bishop N Hille E Morlock M 《Bio-medical materials and engineering》2003,13(4):317-325
In revision surgeries of endoprostheses, the interface between implant and bone cement or bone must be loosened. Conventional tools have many disadvantages because of their size and limited range. Taking advantage of the selective and athermic cutting process, a plain water jet is already used in order to cut soft tissues. This study investigates the possibilities of both a plain and an abrasive water jet as cutting tools for revision surgery. Samples of the mid-diaphysis of human femora and bone cement (CMW3) were cut with a plain water jet (PWJ) and an abrasive water jet (AWJ) at two different jet-to-surface angles (30 degrees,90 degrees ) and at five different pressure levels (30, 40, 50, 60, 70 MPa). For a PWJ a selective pressure range was identified, where only bone cement was cut. Injecting a bio-compatible abrasive (lactose) to the jet stream resulted in significantly higher cut depths in both materials. Material removal in bone was significantly less at the smaller jet-to-surface angle for both techniques. No clear selectivity between bone and bone cement was observed for application of the AWJ. However, the material removal rate was significantly higher for bone cement than for bone at all pressure levels. The results indicate that an AWJ might be an alternative tool for cement removal. The possibility for localised cutting at interfaces could be an advantage for revision of a non-cemented prosthesis. 相似文献
75.
Klose A Peters H Hoffmeyer S Buske A Lüder A Hess D Lehmann R Nürnberg P Tinschert S 《American journal of medical genetics》1999,83(1):6-12
We report on two independent alterations of the NF1 gene in a three-generation kindred with neurofibromatosis type 1 (NF1). Using temperature gradient gel electrophoresis (TGGE) in a mutation analysis of exon 31 of the NF1 gene we detected the previously reported nonsense mutation R1947X. This C-to-T transition at codon 1947 in exon 31 is considered to represent a mutation "hot spot" of the NF1 gene due to 5mCpG deamination. All living family members together with their genomic DNA were included in this investigation. However, the mutation R1947X was absent from two undoubtedly affected siblings of the propositus. Another NF1 mutation (889-2A-->G) was identified in the two sibs by the protein truncation test (PTT). The novel splice site mutation 889-2A-->G results in a skip of NF1 exon 7 during splicing and protein truncation due to frameshift. The two NF1 alterations are linked to different paternal haplotypes. In our study of a three-generation kindred, R1947X represents a de novo mutation whereas 889-2A-->G is an inherited splice mutation. Implications for phenotype variation are discussed. 相似文献
76.
Induction of NO synthesis in macrophages by Newcastle disease virus is associated with activation of nuclear factor-{kappa}B 总被引:3,自引:0,他引:3
Umansky Victor; Shatrov Vladimir A.; Lehmann Volker; Schirrmacher Volker 《International immunology》1996,8(4):491-498
Newcastle disease virus (NDV) has received much attention recentlybecause of its non-specific immune stimulating potential andits various anti-tumor activities. Here we describe that NDVinduces synthesis of NO and causes an activation of nuclearfactor-kB (NF-kB) In murine macrophages. These reactions werepart of an activation process which included also stimulationof adenosine deaminase and inhibition of 5'-nucleotidase. NDV-mediatedNO synthesis and NF-kB activation were blocked by an antioxidant(butylated hydroxyanisole), by an inhibitor of protein tyrosinekinase (genistein) and of protein kinase A (H-89), but not byan inhibitor of protein kinase C (staurosporin). These datasuggest that signalling requirements of NF-kB activation andNO production in NDV-treated macrophages are similar. 相似文献
77.
In the process of developing global health informatics education, a common understanding of educational outcomes is required. Therefore, an educational framework for health informatics professionals is desirable to support student mobility, trans-national and borderless education. Nurses form a significant part of the health workforce and need to be properly educated for their roles in health informatics. To ascertain their perceptions of needs and priorities, we developed a web-based questionnaire and surveyed Australian nurses on the preferred knowledge/skills set for health informatics professionals. Among others, the questionnaire is based on the International Medical Informatics Association's (IMIA) set of recommendations on education and IMIA's scientific map. Benner's five levels of competencies were applied to measure the degree of competency required for each skill/knowledge. Altogether, 82 Australian nurses completed the questionnaire. The nurses' perceived degree of competency required for a total of 74 specific skills and knowledge in five skill categories is presented in this paper as well as the overall results for each of the five categories. Further, significant differences between the nurses' primary roles and primary interest in health informatics are discussed. The development of a comprehensive health informatics education framework needs to take into account nurses as well as other health professionals. Repeating the survey in other countries and for various professions is essential to develop an international educational framework. 相似文献
78.
T cell reactivity in neonates from an East and a West German city--results of the LISA study 总被引:1,自引:0,他引:1
Lehmann I Thoelke A Weiss M Schlink U Schulz R Diez U Sierig G Emmrich F Jacob B Belcredi P Bolte G Heinrich J Herbarth O Wichmann HE Borte M 《Allergy》2002,57(2):129-136
BACKGROUND: Within an ongoing birth cohort study (LISA) the cytokine production of cord blood T cells was compared between neonates from Leipzig (East Germany) and Munich (West Germany). The aim of this study was to analyse regional differences and influencing factors of the immune status. METHODS: Cytokine production was measured in a randomly selected subgroup of 158 children from the LISA (Life style - Immune system - Allergy) cohort by intracellular cytokine staining. Information on family "atopy" history (FAH) and home characteristics was obtained from questionnaires. RESULTS: Reduced numbers of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) producing T cells were found in association with biparental FAH and housing renovation during pregnancy. In addition, cytokine production was influenced by season. In Munich, the frequency of biparental FAH and of renovation measures during pregnancy was significantly higher as compared to Leipzig. Neonates from Munich showed significantly decreased amounts of IFN-gamma and TNF-alpha and elevated levels of interleukin-4 (IL-4) producing T cells. Differences in cytokine production between Munich and Leipzig were influenced by season (IL-4) and housing renovation (IFN-gamma, TNF-alpha). CONCLUSIONS: Since differences in the T cell cytokine production of neonates in Munich and Leipzig are independent from FAH our findings may provide evidence for the impact of environmental factors upon the fetal immune system. 相似文献
79.
Helicobacter pylori infection 总被引:1,自引:0,他引:1
80.
Age-related changes in peripheral nerves 总被引:1,自引:0,他引:1
J Lehmann 《Zentralblatt für allgemeine Pathologie und pathologische Anatomie》1986,131(3):219-227
Semi-thin sections of the sural nerve from 200 autopsy specimens taken from individuals of both sexes, ages 10 to 91 were morphologically examined. Thickness of the endoneurial capillary walls, and of the perineurium, number of endoneurial capillaries, myelinated fiber density and distribution of myelinated fibers were determined. An additional ultrastructural examination of selected nerves with characteristic values was performed. The analysis revealed a statistically significant age dependence for the investigated features. Increasing age was associated with decreased myelinated fiber density and decreased number of endoneurial capillaries. There was an age dependent increase in the thickness of capillary walls and the perineurium as well as increasing loss of large myelinated fibers. The findings were discussed and compared with similar results from the literature. Age related changes in peripheral nerves have to be interpreted as the result of the cumulative, life-long effect of various pathogenic factors, modified by genetic determinants and by a gradual decrease in regenerative capacity. 相似文献