全文获取类型
收费全文 | 2312篇 |
免费 | 104篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 28篇 |
儿科学 | 73篇 |
妇产科学 | 114篇 |
基础医学 | 298篇 |
口腔科学 | 115篇 |
临床医学 | 113篇 |
内科学 | 465篇 |
皮肤病学 | 18篇 |
神经病学 | 169篇 |
特种医学 | 98篇 |
外国民族医学 | 1篇 |
外科学 | 413篇 |
综合类 | 14篇 |
一般理论 | 2篇 |
预防医学 | 86篇 |
眼科学 | 23篇 |
药学 | 185篇 |
中国医学 | 2篇 |
肿瘤学 | 202篇 |
出版年
2021年 | 36篇 |
2020年 | 21篇 |
2019年 | 26篇 |
2018年 | 31篇 |
2017年 | 17篇 |
2016年 | 24篇 |
2015年 | 28篇 |
2014年 | 59篇 |
2013年 | 71篇 |
2012年 | 116篇 |
2011年 | 103篇 |
2010年 | 61篇 |
2009年 | 59篇 |
2008年 | 128篇 |
2007年 | 92篇 |
2006年 | 114篇 |
2005年 | 108篇 |
2004年 | 116篇 |
2003年 | 112篇 |
2002年 | 132篇 |
2001年 | 63篇 |
2000年 | 62篇 |
1999年 | 66篇 |
1998年 | 23篇 |
1997年 | 18篇 |
1996年 | 24篇 |
1995年 | 23篇 |
1994年 | 20篇 |
1992年 | 35篇 |
1991年 | 37篇 |
1990年 | 28篇 |
1989年 | 41篇 |
1988年 | 29篇 |
1987年 | 36篇 |
1986年 | 34篇 |
1985年 | 19篇 |
1983年 | 26篇 |
1982年 | 14篇 |
1981年 | 18篇 |
1980年 | 18篇 |
1979年 | 15篇 |
1978年 | 19篇 |
1977年 | 15篇 |
1975年 | 21篇 |
1973年 | 22篇 |
1972年 | 18篇 |
1970年 | 19篇 |
1969年 | 17篇 |
1967年 | 18篇 |
1966年 | 13篇 |
排序方式: 共有2419条查询结果,搜索用时 15 毫秒
71.
The E5 proteins of bovine papillomavirus type 1 (BPV-1) and human papillomavirus type 16 (HPV-16) are small (44-83 amino acids), hydrophobic polypeptides that localize to membranes of the Golgi apparatus and endoplasmic reticulum, respectively. While the oncogenic properties of BPV-1 E5 have been characterized in detail, less is known about HPV-16 E5 due to its low expression in mammalian cells. Using codon-optimized HPV-16 E5 DNA, we have generated stable fibroblast cell lines that express equivalent levels of epitope-tagged BPV-1 and HPV-16 E5 proteins. In contrast to BPV-1 E5, HPV-16 E5 does not activate growth factor receptors, phosphoinositide 3-kinase or c-Src, and fails to induce focus formation, although it does promote anchorage-independent growth in soft agar. These variant activities are apparently unrelated to differences in intracellular localization of the E5 proteins since retargeting HPV-16 E5 to the Golgi apparatus does not induce focus formation. 相似文献
72.
DFNA54, a third locus for low-frequency hearing loss 总被引:1,自引:0,他引:1
Gürtler N Kim Y Mhatre A Schlegel C Mathis A Lalwani AK 《Journal of molecular medicine (Berlin, Germany)》2004,82(11):775-780
Nonsyndromic hereditary hearing impairment (NSHHI) is a highly heterogeneous disorder with more than 90 loci mapped, of which nearly one-half of the responsible genes are identified. In dominant NSSHI hearing loss is typically biased towards the high frequencies while low-frequency hearing loss is unusual. Only two NSHHI loci, DFNA1 and DFNA6/14/38, are associated with predominantly low- frequency loss. We mapped the loci harboring the gene responsible for autosomal dominant low-frequency hearing loss in a multigenerational family. The pedigree of a Swiss family with low-frequency hearing loss was established. Using genomic DNA, DFNA1 and DFNA6/14/38 were excluded by linkage analysis or by direct sequencing of the responsible gene. Genome-wide linkage analysis was performed using commercially available microsatellite markers. Two-point linkage analysis demonstrated linkage to chromosome 5q31, the locus for DFNA15, with a lod score of 6.32 at recombination fraction =0 for marker D5S436. Critical recombinations were seen at markers D5S1972 and D5S410. Sequencing of the corresponding gene POU4F3 yielded no pathogenic mutation segregating with the affected members. In addition to Wolfram syndrome gene 1 (DFNA6/14/38) and diaphanous (DFNA1) there is evidence for a third gene involved in low-frequency hearing loss located at DFNA15. Because of the differences in auditory phenotype and the absence of pathogenic mutation in the coding region of POU4F3 it is likely that there is a second gene in 5q31, designated DFNA54, associated with NSHHI. 相似文献
73.
Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model 总被引:1,自引:0,他引:1
Abdelaziz AI Segaric J Bartsch H Petzhold D Schlegel WP Kott M Seefeldt I Klose J Bader M Haase H Morano I 《Journal of molecular medicine (Berlin, Germany)》2004,82(4):265-274
Most patients with hypertrophic cardiomyopathy and congenital heart diseases express the atrial essential myosin light chains (ALC-1) in their ventricles, partially replacing the ventricular essential light chains (VLC-1). This VLC-1/ALC-1 isoform shift is correlated with an increase in cross-bridge cycling kinetics as measured using skinned fibers from the hypertrophied ventricles of human hearts.To study the functional importance of hALC-1 in the intact perfused heart, we generated a transgenic rat model (TGR) overexpressing hALC-1 in the heart. Twelve-week-old TGR rats expressed 17±4 g hALC-1 per mg of whole SDS-soluble protein. Their perfused heart contractility parameters were evaluated using the Langendorff preparation. Expression of hALC-1 was accompanied by statistically significant improvements (P<0.001) in the contractile parameters of the hearts of the TGR compared to the age matched control (WKY) animals, represented by increases from 20.8±2.3 to 45.1±3.6 mmHg/g heart weight in the developed left ventricular pressure, 1,035.7±89.8 to 2,181±135.4 mmHg/s in the contraction rate, and 713±60.2 to 1,364±137.4 mmHg/s in the relaxation rate in the WKY and the TGR groups respectively. Characterizing the functional effects of hALC-1 at the whole organ level represents a step towards gene therapy of heart failure. 相似文献
74.
Marlovits S Hombauer M Tamandl D Vècsei V Schlegel W 《International journal of molecular medicine》2004,13(2):281-287
Human articular chondrocytes (HACs) were isolated from cartilage samples of normal joints and cultivated in monolayer for 56 days. Collagen type I, II, IX, aggrecan, and versican expression was quantified by real-time polymerase chain reaction (PCR). The expression of the genes was highly time-dependent and changed over the culture time. Collagen type I was not present at the beginning of the culture and increased 100-fold during the culture time. Collagen type II and IX expression was found during the entire culture period and decreased more than 100-fold. Aggrecan expression was downregulated 100-fold whereas versican expression increased 10 times. Indices of cell differentiation, defined as ratios of collagen type II to I (CII/I), collagen type IX to I (CIX/I), and aggrecan to versican (Agg/Ver), were significantly higher at the beginning of the culture and decreased over the culture period. The CII/I and CIX/I ratios formed three phases, with a plateau at the beginning, followed by a transition phase and a steady state at the end of the culture time, whereas the Agg/Ver ratio declined constantly. The accurate quantitative assessment of extracellular matrix gene expression in samples of chondrocytes taken from monolayer culture can be used to monitor chondrocyte metabolism as well as changes in the cell differentiation status. 相似文献
75.
Al-Otaiby M Tassi E Schmidt MO Chien CD Baker T Salas AG Xu J Furlong M Schlegel R Riegel AT Wellstein A 《The American journal of pathology》2012,180(4):1474-1484
The nuclear receptor coactivator amplified in breast cancer 1 (AIB1/SRC-3) has a well-defined role in steroid and growth factor signaling in cancer and normal epithelial cells. Less is known about its function in stromal cells, although AIB1/SRC-3 is up-regulated in tumor stroma and may, thus, contribute to tumor angiogenesis. Herein, we show that AIB1/SRC-3 depletion from cultured endothelial cells reduces their proliferation and motility in response to growth factors and prevents the formation of intact monolayers with tight junctions and of endothelial tubes. In AIB1/SRC-3(+/-) and (-/-) mice, the angiogenic responses to subcutaneous Matrigel implants was reduced by two-thirds, and exogenously added fibroblast growth factor (FGF) 2 did not overcome this deficiency. Furthermore, AIB1/SRC-3(+/-) and (-/-) mice showed similarly delayed healing of full-thickness excisional skin wounds, indicating that both alleles were required for proper tissue repair. Analysis of this defective wound healing showed reduced recruitment of inflammatory cells and macrophages, cytokine induction, and metalloprotease activity. Skin grafts from animals with different AIB1 genotypes and subsequent wounding of the grafts revealed that the defective healing was attributable to local factors and not to defective bone marrow responses. Indeed, wounds in AIB1(+/-) mice showed reduced expression of FGF10, FGFBP3, FGFR1, FGFR2b, and FGFR3, major local drivers of angiogenesis. We conclude that AIB1/SRC-3 modulates stromal cell responses via cross-talk with the FGF signaling pathway. 相似文献
76.
Ponader S Vairaktaris E Heinl P Wilmowsky CV Rottmair A Körner C Singer RF Holst S Schlegel KA Neukam FW Nkenke E 《Journal of biomedical materials research. Part A》2008,84(4):1111-1119
The aim of the study was to assess the suitability of different Ti-6Al-4V surfaces produced by the electron beam melting (EBM) process as matrices for attachment, proliferation, and differentiation of human fetal osteoblasts (hFOB 1.19). Human osteoblasts were cultured in vitro on smooth and rough-textured Ti-6Al-4V alloy disks. By means of cell number and vitality and SEM micrographs cell attachment and proliferation were observed. The differentiation rate was examined by using quantitative real-time PCR analysis for the gene expression of alkaline phosphatase (ALP), type I collagen (Coll-I), bone sialoprotein (BSP) and osteocalcin (OC). After 3 days of incubation there was a significant higher vitality (p < 0.02) and proliferation (p < 0.02) of hFOB cells on smooth surfaces (R(a) = 0.077 microm) and compact surfaces with adherent partly molten titanium particles on the surface (R(a) = 24.9 microm). On these samples cells spread over almost the whole surface. On porous surfaces with higher R(a) values, cell proliferation was reduced significantly. Quantitative real-time PCR analysis showed that the expression of osteogenic differentiation markers was not influenced by surface characteristics. Gene expression did not differ more than twofold for the different samples. Compact titanium samples with adherent partly molten titanium particles on the surface (R(a) = 24.9 microm) fabricated by the EBM process turned out to be best suited for cell proliferation, while highly rough surfaces (R(a) >/= 56.9 microm) reduced proliferation of hFOB cells. Surface characteristics of titanium can easily be changed by EBM in order to further improve proliferation. 相似文献
77.
Jagu S Malandro N Kwak K Yuan H Schlegel R Palmer KE Huh WK Campo MS Roden RB 《Virology》2011,420(1):43-50
It is unclear what level of neutralizing antibody is sufficient to protect cattle from experimental bovine papillomavirus type 4 (BPV4) challenge. Markedly lower, and often undetected, serum neutralizing antibody titers were associated with protection in cattle vaccinated with BPV4 L2 as compared to L1 VLP. We hypothesized that vaccination with concatemers of the N-terminal protective epitopes of L2 derived from multiple animal papillomavirus types would enhance the breadth and strength of immunity. Therefore we generated a multimeric L2 antigen derived from three bovine and three canine papillomavirus types with divergent phenotypes and purified it from bacteria. Mice vaccinated three times with this six type L2 vaccine formulated in alum or RIBI adjuvant generated robust serum neutralizing antibody titers against BPV1, BPV4 and canine oral papillomavirus (COPV). Furthermore, vaccination with this six type L2 vaccine formulated in adjuvant, like BPV1 L1 VLP, protected the mice from experimental challenge with BPV1 pseudovirus. 相似文献
78.
Eyrich M Schreiber SC Wollny G Ziegler H Schlenker R Koch-Büttner K Wölfl M Schlegel PG Schilbach K 《European journal of immunology》2011,41(12):3596-3603
T-cell re-constitution after allogeneic stem cell transplantation (alloSCT) is often dampened by the slow differentiation of human peripheral blood CD34(+) (huCD34(+) ) hematopoietic stem cells (HSCs) into mature T cells. This process may be accelerated by the co-transfer of in vitro-pre-differentiated committed T/NK-lymphoid progenitors (CTLPs). Here, we analysed the developmental potential of huCD34(+) HSCs compared with CTLPs from a third-party donor in a murine NOD-scid IL2Rγ(null) model of humanised chimeric haematopoiesis. CTLPs (CD34(+) lin(-) CD45RA(+) CD7(+) ) could be generated in vitro within 10 days upon co-culture of huCD34(+) or cord blood CD34(+) (CB-CD34) HSCs on murine OP9/N-DLL-1 stroma cells but not in a novel 3-D cell-culture matrix with DLL-1(low) human stroma cells. In both in vitro systems, huCD34(+) and CB-CD34(+) HSCs did not give rise to mature T cells. Upon transfer into 6-wk-old immune-deficient mice, CTLPs alone did not engraft. However, transplantation of CTLPs together with huCD34(+) HSCs resulted in rapid T-cell engraftment in spleen, bone marrow and thymus at day 28. Strikingly, at this early time point mature T cells originated exclusively from CTLPs, whereas descendants of huCD34(+) HSCs still expressed a T-cell-precursor phenotype (CD7(+) CD5(+) CD1a(+/-) ). This strategy to enhance early T-cell re-constitution with ex vivo-pre-differentiated T-lymphoid progenitors could bridge the gap until full T-cell recovery in severely immunocompromised patients after allogeneic stem cell transplantation. 相似文献
79.
80.
Schlegel P Hayes JS Frauchiger VM Gasser B Wieling R Textor M Richards RG 《Journal of biomedical materials research. Part B, Applied biomaterials》2009,90(1):26-34
Implant loosening is an unresolved complication associated with prosthetics. Previous studies report improved osseointegration with hydroxyapatite (HA) or tri-calcium phosphate coatings. Unfortunately, the brittleness and low strength of these coatings in adhesion to the implant or internal cohesion is problematic, restricting their use. Anodic plasma-chemical (APC) treatment, an advanced anodisation method, allows for porous oxide layer formation with incorporation of calcium and phosphate directly into the oxide. This produces superior adhesive strength than a conventional coating of calcium phosphate offering potential for long-term osseointegration. Although the cytocompatibility of several APC treatments have been previously shown, this study was the first to investigate the biocompatibility and osteoconductivity of APC surfaces in vivo when compared with standard HA coated and noncoated commercially pure titanium implant cortical screws. Sample screws were implanted in female Swiss alpine sheep for 12 weeks. Bone remodelling in situ, differences in bone apposition resulting in cortical thickening as well as peak removal torque measurements were assessed. We found no significant differences between the tested coatings and no delamination was observed with any of the APC-treated surfaces. The results suggest that APC-treated samples have similar biological performance to HA-coated screws. In our opinion, APC treatment, which also has superior binding strength to the base metal compared with standard HA coatings as well as similar biocompatibility as shown here, holds great potential for biomedical applications. Now that the in vivo biocompatibility has been proven, the work is being extended to more challenging in vivo models. 相似文献