全文获取类型
收费全文 | 2776篇 |
免费 | 200篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 12篇 |
儿科学 | 63篇 |
妇产科学 | 91篇 |
基础医学 | 577篇 |
口腔科学 | 22篇 |
临床医学 | 244篇 |
内科学 | 618篇 |
皮肤病学 | 29篇 |
神经病学 | 241篇 |
特种医学 | 82篇 |
外科学 | 200篇 |
综合类 | 12篇 |
一般理论 | 2篇 |
预防医学 | 183篇 |
眼科学 | 37篇 |
药学 | 333篇 |
2篇 | |
中国医学 | 11篇 |
肿瘤学 | 223篇 |
出版年
2024年 | 1篇 |
2023年 | 23篇 |
2022年 | 58篇 |
2021年 | 99篇 |
2020年 | 70篇 |
2019年 | 87篇 |
2018年 | 98篇 |
2017年 | 72篇 |
2016年 | 75篇 |
2015年 | 91篇 |
2014年 | 133篇 |
2013年 | 151篇 |
2012年 | 232篇 |
2011年 | 228篇 |
2010年 | 126篇 |
2009年 | 98篇 |
2008年 | 222篇 |
2007年 | 233篇 |
2006年 | 183篇 |
2005年 | 170篇 |
2004年 | 141篇 |
2003年 | 126篇 |
2002年 | 115篇 |
2001年 | 13篇 |
2000年 | 3篇 |
1999年 | 23篇 |
1998年 | 18篇 |
1997年 | 15篇 |
1996年 | 31篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 7篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有2982条查询结果,搜索用时 15 毫秒
11.
Cation channels,cell volume and the death of an erythrocyte 总被引:8,自引:0,他引:8
Lang F Lang KS Wieder T Myssina S Birka C Lang PA Kaiser S Kempe D Duranton C Huber SM 《Pflügers Archiv : European journal of physiology》2003,447(2):121-125
Similar to a variety of nucleated cells, human erythrocytes activate a non-selective cation channel upon osmotic cell shrinkage. Further stimuli of channel activation include oxidative stress, energy depletion and extracellular removal of Cl–. The channel is permeable to Ca2+ and opening of the channel increases cytosolic [Ca2+]. Intriguing evidence points to a role of this channel in the elimination of erythrocytes by apoptosis. Ca2+ entering through the cation channel stimulates a scramblase, leading to breakdown of cell membrane phosphatidylserine asymmetry, and stimulates Ca2+-sensitive K+ channels, thus leading to KCl loss and (further) cell shrinkage. The breakdown of phosphatidylserine asymmetry is evidenced by annexin binding, a typical feature of apoptotic cells. The effects of osmotic shock, oxidative stress and energy depletion on annexin binding are mimicked by the Ca2+ ionophore ionomycin (1 µM) and blunted in the nominal absence of extracellular Ca2+. Nevertheless, the residual annexin binding points to additional mechanisms involved in the triggering of the scramblase. The exposure of phosphatidylserine at the extracellular face of the cell membrane stimulates phagocytes to engulf the apoptotic erythrocytes. Thus, sustained activation of the cation channels eventually leads to clearance of affected erythrocytes from peripheral blood. Susceptibility to annexin binding is enhanced in several genetic disorders affecting erythrocyte function, such as thalassaemia, sickle-cell disease and glucose-6-phosphate dehydrogenase deficiency. The enhanced vulnerability presumably contributes to the shortened life span of the affected erythrocytes. Beyond their role in the limitation of erythrocyte survival, cation channels may contribute to the triggering of apoptosis in nucleated cells exposed to osmotic shock and/or oxidative stress. 相似文献
12.
Knutsen T Pack S Petropavlovskaja M Padilla-Nash H Knight C Mickley LA Ried T Elwood PC Roberts SJ 《Genes, chromosomes & cancer》2003,37(3):270-281
Cytogenetic studies of patients with therapy-induced acute myeloid leukemia (t-AML) have demonstrated whole chromosome loss or q-arm deletion of chromosomes 5 and/or 7 in a majority of cases. We have established two cell lines, SAML-1 and SAML-2, from two patients who developed t-AML after radiation and chemotherapy for Hodgkin disease. In both cases, the leukemia cells contained 5q deletions. SAML-1 has 58 chromosomes and numerous abnormalities, including der(1)(1qter-->1p22::5q31-->5qter), der(5)(5pter-->5q22::1p22-->1pter), +8, der(13)i(13)(q10)del(13)(q11q14.1), and t(10;11). Fluorescence in situ hybridization (FISH) with unique sequence probes for the 5q31 region showed loss of IL4, IL5, IRF1, and IL3, and translocation of IL9, DS5S89, EGR1, and CSFIR to 1p. SAML-2 has 45 chromosomes, del(5)(q11.2q31) with a t(12;13)ins(12;5), leading to the proximity of IRF1 and RB1, and complex translocations of chromosomes 8 and 11, resulting in amplification of MYC and MLL. Comparative genomic hybridization and spectral karyotyping were consistent with the G-banding karyotype and FISH analyses. Because a potential tumor suppressor(s) in the 5q31 region has yet to be identified, these cell lines should prove useful in the study of the mechanisms leading to the development of t-AML. 相似文献
13.
Renal glomerulogenesis in medaka fish, Oryzias latipes 总被引:2,自引:0,他引:2
Svetlana Fedorova Rieko Miyamoto Tomohiro Harada Sumio Isogai Hisashi Hashimoto Kenjiro Ozato Yuko Wakamatsu 《Developmental dynamics》2008,237(9):2342-2352
We provide an overview of glomerulogenesis in medaka from the embryo to the adult by means of in situ hybridization with the wt1 gene as a marker as well as histology and three-dimensional images. The pronephric glomus starts to develop in the intermediate mesoderm during early somitogenesis, is completed before hatching, and persists throughout the lifetime of the fish. Within 5 days after hatching, mesonephric glomerulus formation begins in the caudomedial end of the pronephric sinus and duct area. The number of glomeruli reaches approximately 200-300 in each kidney within 2 months after hatching. wt1 expression during nephron maturation served as a marker for the formation of the mesenchymal condensate and the nephrogenic body. Existence of mesenchymal condensates and persistence of wt1 expression in the adult kidney suggest that the mesonephros retains precursor cells that may be capable of contributing to neoglomerulogenesis during adulthood. Developmental Dynamics 237:2342-2352, 2008. (c) 2008 Wiley-Liss, Inc. 相似文献
14.
15.
Yulia Vistoropsky Svetlana Trofimov Ia Pantsulaia Gregory Livshits 《Annals of human genetics》2006,70(6):749-758
In our research we examined the contribution of putative genetic sources on interindividual variation and cross-sectional correlations of several adhesion molecules, including intracellular (ICAM-1) and vascular cell adhesion molecules (VCAM-1) and E-selectin, in a population-based sample of ethnically homogeneous families of European origin. The plasma levels of these molecules were measured in 947 apparently healthy individuals from 217 nuclear families. Quantitative statistical-genetic analysis implementing the model fitting technique revealed significant parent/offspring and sibling correlations (p < 0.01) for all three molecules. The putative genetic effects explained 55.2 ± 7.2% (VCAM-1), 63.3 ± 7.5% (ICAM) and 63.8 ± 8.1% (E-selectin) of the variation. Common family environmental factors also significantly influenced the variation of E-selectin (13%) and VCAM-1 (28.6%). The main results of our bivariate analysis showed that the observed phenotypic correlations between ICAM-1 and VCAM-1, and between ICAM-1 and E-selectin, were mostly attributable to shared environmental factors ( rE = 0.896 and 0.737, respectively; p < 0.01). However, the correlation between VCAM-1 and E-selectin was likely caused by common genetic effects (rG = 0.334, p < 0.05) . Our results show that familial clustering of adhesion molecules is likely due to strong genetic effects, supplemented with shared environmental factors. 相似文献
16.
Shebzukhov YV Koroleva EP Khlgatian SV Lagarkova MA Meshcheryakov AA Lichinitser MR Karbach J Jager E Kuprash DV Nedospasov SA 《Immunology letters》2005,100(1):88-93
Thymidylate synthase (TYMS), the critical enzyme for DNA synthesis and a target for chemotherapy, was recently characterized as an oncogene and a potential target for specific immunotherapy. Here we report TYMS-specific antibody response in a fraction of colon cancer patients. Humoral immune response to TYMS is induced by chemotherapy using TYMS inhibitors, such as 5-fluorouracil (5-FU), and may be associated with tumor burden. Therefore, TYMS may serve as a useful serological biomarker for monitoring the course of disease and treatment in cancer patients. 相似文献
17.
Sau W Cheung Chad A Shaw Wei Yu Jiangzham Li Zhishuo Ou Ankita Patel Svetlana A Yatsenko Mitchell L Cooper Patti Furman Pawel Stankiewicz Pawal Stankiewicz James R Lupski A Craig Chinault Arthur L Beaudet 《Genetics in medicine》2005,7(6):422-432
PURPOSE: We developed a microarray for clinical diagnosis of chromosomal disorders using large insert genomic DNA clones as targets for comparative genomic hybridization (CGH). METHODS: The array contains 362 FISH-verified clones that span genomic regions implicated in over 40 known human genomic disorders and representative subtelomeric clones for each of the 41 clinically relevant human chromosome telomeres. Three or four clones from almost all deletion or duplication genomic regions and three or more clones for each subtelomeric region were included. We tested chromosome microarray analysis (CMA) in a masked fashion by examining genomic DNA from 25 patients who were previously ascertained in a genetic clinic and studied by conventional cytogenetics. A novel software package implemented in the R statistical programming language was developed for normalization, visualization, and inference. RESULTS: The CMA results were entirely consistent with previous cytogenetic and FISH findings. For clone by clone analysis, the sensitivity was estimated to be 96.7% and the specificity was 99.1%. Major advantages of this selected human genome array include the following: interrogation of clinically relevant genomic regions, the ability to test for a wide range of duplication and deletion syndromes in a single analysis, the ability to detect duplications that would likely be undetected by metaphase FISH, and ease of confirmation of suspected genomic changes by conventional FISH testing currently available in the cytogenetics laboratory. CONCLUSION: The array is an attractive alternative to telomere FISH and locus-specific FISH, but it does not include uniform coverage across the arms of each chromosome and is not intended to substitute for a standard karyotype. Limitations of CMA include the inability to detect both balanced chromosome changes and low levels of mosaicism. 相似文献
18.
Allcock RJ Windsor L Gut IG Kucharzak R Sobre L Lechner D Garnier JG Baltic S Christiansen FT Price P 《Human mutation》2004,24(6):517-525
The region spanning the tumor necrosis factor (TNF) cluster in the human major histocompatibility complex (MHC) has been implicated in susceptibility to numerous immunopathological diseases, including type 1 diabetes mellitus and rheumatoid arthritis. However, strong linkage disequilibrium across the MHC has hampered the identification of the precise genes involved. In addition, the observation of "blocks" of DNA in the MHC within which recombination is very rare, limits the resolution that may be obtained by genotyping individual SNPs. Hence a greater understanding of the haplotypes of the block spanning the TNF cluster is necessary. To this end, we genotyped 32 human leukocyte antigen (HLA)-homozygous workshop cell lines and 300 healthy control samples for 19 coding and promoter region SNPs spanning 45 kb in the central MHC near the TNF genes. The workshop cell lines defined 11 SNP haplotypes that account for approximately 80% of the haplotypes observed in the 300 control individuals. Using the control individuals, we defined a further six haplotypes that account for an additional 10% of donors. We show that the 17 haplotypes of the "TNF block" can be identified using 15 SNPs. 相似文献
19.
Genetic basis for individual variations in pain perception and the development of a chronic pain condition 总被引:11,自引:0,他引:11
Diatchenko L Slade GD Nackley AG Bhalang K Sigurdsson A Belfer I Goldman D Xu K Shabalina SA Shagin D Max MB Makarov SS Maixner W 《Human molecular genetics》2005,14(1):135-143
Pain sensitivity varies substantially among humans. A significantpart of the human population develops chronic pain conditionsthat are characterized by heightened pain sensitivity. We identifiedthree genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase(COMT) that we designated as low pain sensitivity (LPS), averagepain sensitivity (APS) and high pain sensitivity (HPS). We showthat these haplotypes encompass 96% of the human population,and five combinations of these haplotypes are strongly associated(P=0.0004) with variation in the sensitivity to experimentalpain. The presence of even a single LPS haplotype diminishes,by as much as 2.3 times, the risk of developing myogenous temporomandibularjoint disorder (TMD), a common musculoskeletal pain condition.The LPS haplotype produces much higher levels of COMT enzymaticactivity when compared with the APS or HPS haplotypes. Inhibitionof COMT in the rat results in a profound increase in pain sensitivity.Thus, COMT activity substantially influences pain sensitivity,and the three major haplotypes determine COMT activity in humansthat inversely correlates with pain sensitivity and the riskof developing TMD. 相似文献
20.
Jovanović I Stefanović N Antić S Ugrenović S Djindjić B Vidović N 《Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia》2004,109(1):19-33
Psammoma bodies are one of many choroid plexus aging changes which origin is still enigma for the scientists. During our investigation psammoma bodies were studied on 30 postmortem brains by light microscopy. They stained red with HE, and were PAS and AB PAS positive. The largest number of lamellas were stained blue with Mallory's connective tissue stain, except peripheral and next to the center lamella which stained red. During the aging, psammoma bodies became larger and more irregular, which was followed with group area and perimeter, single psammoma body average area and average perimeter, average diameter and contour index increase. Psammoma bodies mearged in the second and the third age group and mearging process led to larger and more irregular structures formation. The results of this investigation suggest that psammoma bodies are more frequent in choroid plexus of healthy older people and during the aging they obtain larger dimensions, more irregular contours, which is the result of their mutual mearging. 相似文献