全文获取类型
收费全文 | 2050篇 |
免费 | 138篇 |
国内免费 | 69篇 |
专业分类
耳鼻咽喉 | 9篇 |
儿科学 | 11篇 |
妇产科学 | 27篇 |
基础医学 | 847篇 |
口腔科学 | 18篇 |
临床医学 | 95篇 |
内科学 | 342篇 |
皮肤病学 | 11篇 |
神经病学 | 35篇 |
特种医学 | 40篇 |
外科学 | 104篇 |
综合类 | 271篇 |
现状与发展 | 1篇 |
预防医学 | 92篇 |
眼科学 | 6篇 |
药学 | 138篇 |
中国医学 | 10篇 |
肿瘤学 | 200篇 |
出版年
2024年 | 2篇 |
2023年 | 31篇 |
2022年 | 28篇 |
2021年 | 99篇 |
2020年 | 57篇 |
2019年 | 58篇 |
2018年 | 51篇 |
2017年 | 41篇 |
2016年 | 67篇 |
2015年 | 100篇 |
2014年 | 101篇 |
2013年 | 93篇 |
2012年 | 90篇 |
2011年 | 119篇 |
2010年 | 90篇 |
2009年 | 126篇 |
2008年 | 113篇 |
2007年 | 113篇 |
2006年 | 93篇 |
2005年 | 101篇 |
2004年 | 109篇 |
2003年 | 77篇 |
2002年 | 53篇 |
2001年 | 51篇 |
2000年 | 39篇 |
1999年 | 36篇 |
1998年 | 39篇 |
1997年 | 44篇 |
1996年 | 36篇 |
1995年 | 24篇 |
1994年 | 32篇 |
1993年 | 17篇 |
1992年 | 14篇 |
1991年 | 16篇 |
1990年 | 13篇 |
1989年 | 9篇 |
1988年 | 8篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 9篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 8篇 |
1979年 | 5篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
排序方式: 共有2257条查询结果,搜索用时 46 毫秒
991.
Robinson CM Singh G Henquell C Walsh MP Peigue-Lafeuille H Seto D Jones MS Dyer DW Chodosh J 《Virology》2011,409(2):141-147
Adenoviral infections are typically acute, self-limiting, and not associated with death. However, we present the genomic and bioinformatics analysis of a novel recombinant human adenovirus (HAdV-D56) isolated in France that caused a rare neonatal fatality, and keratoconjunctivitis in three health care workers who cared for the neonate. Whole genome alignments revealed the expected diversity in the penton base, hexon, E3, and fiber coding regions, and provided evidence for extensive recombination. Bootscan analysis confirmed recombination between HAdV-D9, HAdV-D26, HAdV-D15, and HAdV-D29 in the penton base and hexon proteins, centered around hypervariable loops within the putative proteins. Protein structure analysis of the fiber coding region revealed similarity with HAdV-D8, HAdV-D9, and HAdV-D53, possibly accounting for the ocular tropism of the virus. Based on these data, this virus appears to be a new HAdV-D type (HAdV-D56), underscoring the importance of recombination events in human adenovirus evolution and the emergence of new adenovirus pathogens. 相似文献
992.
In the ten years since the discovery of activation-induced cytidine deaminase (AID) there has been considerable effort to understand the mechanisms behind this enzyme's ability to target and modify immunoglobulin genes leading to somatic hypermutation and class switch recombination. While the majority of research has focused on mouse and human models of AID function, work on other species, from lamprey to rabbit and sheep, has taught us much about the scope of functions of the AID mutator. This review takes a species-comparative approach to what has been learned about the AID mutator enzyme and its role in humoral immunity. 相似文献
993.
994.
Wilkerson PM Dedes KJ Wetterskog D Mackay A Lambros MB Mansour M Frankum J Lord CJ Natrajan R Ashworth A Reis-Filho JS 《The Journal of pathology》2011,225(1):29-42
The 11q13-q14 locus is frequently amplified in human cancers, with a complex structure harbouring multiple potential oncogenic drivers. The EMSY gene has been proposed as a driver of the third core of the 11q13-q14 amplicon. This gene encodes a protein reported to be a BRCA2-binding partner, which when over-expressed would lead to impairment of BRCA2 functions and could constitute a mechanism for BRCA2 inactivation in non-hereditary breast and ovarian cancers. We hypothesized that if EMSY amplification abrogates BRCA2 functions, cells harbouring this aberration would be unable to elicit competent homologous recombination DNA repair and, therefore, may have increased sensitivity to genotoxic therapies and potent PARP inhibitors. Microarray-based comparative genomic hybridization of cell lines from distinct tumour sites, including breast, ovary, pancreas, oesophagus, lung and the oral cavity, led to the identification of 10 cell lines with EMSY amplification and 18 without. EMSY amplification was shown to correlate with EMSY mRNA levels, although not all cell lines harbouring EMSY amplification displayed EMSY mRNA or protein over-expression. RNA interference-mediated silencing of EMSY did not lead to a reduction in cell viability in tumour models harbouring EMSY amplification. Cell lines with and without EMSY amplification displayed a similar ability to elicit RAD51 foci in response to DNA damaging agents, and similar sensitivity to cisplatin and olaparib. Taken together, this suggests that EMSY is unlikely to be a driver of the 11q13-q14 amplicon and does not have a dominant role in modulating the response to agents targeting cells with defective homologous recombination. 相似文献
995.
Bai H Sun M Ghosh P Hatfull GF Grindley ND Marko JF 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(18):7419-7424
Structural and topological data suggest that serine site-specific DNA recombinases exchange duplex DNAs by rigid-body relative rotation of the two halves of the synapse, mediated by a flat protein-protein interaction surface. We present evidence for this rotational motion for a simple serine recombinase, the Bxb1 phage integrase, from a single-DNA-based supercoil-release assay that allows us to follow crossover site cleavage, rotation, religation, and product release in real time. We have also used a two-DNA braiding-relaxation experiment to observe the effect of synapse rotation in reactions on two long molecules. Relaxation and unbraiding are rapid (averaging 54 and 70 turns/s, respectively) and complete, with no discernible pauses. Nevertheless, the molecular friction associated with rotation is larger than that of type-I topoisomerases in a similar assay. Surprisingly we find that the synapse can stay rotationally "open" for many minutes. 相似文献
996.
997.
998.
Necşulea A Popa A Cooper DN Stenson PD Mouchiroud D Gautier C Duret L 《Human mutation》2011,32(2):198-206
Although mutations that are detrimental to the fitness of organisms are expected to be rapidly purged from populations by natural selection, some disease-causing mutations are present at high frequencies in human populations. Several nonexclusive hypotheses have been proposed to account for this apparent paradox (high new mutation rate, genetic drift, overdominance, or recent changes in selective pressure). However, the factors ultimately responsible for the presence at high frequency of disease-causing mutations are still contentious. Here we establish the existence of an additional process that contributes to the spreading of deleterious mutations: GC-biased gene conversion (gBGC), a process associated with recombination that tends to favor the transmission of GC-alleles over AT-alleles. We show that the spectrum of amino acid-altering polymorphisms in human populations exhibits the footprints of gBGC. This pattern cannot be explained in terms of selection and is evident with all nonsynonymous mutations, including those predicted to be detrimental to protein structure and function, and those implicated in human genetic disease. We present simulations to illustrate the conditions under which gBGC can extend the persistence time of deleterious mutations in a finite population. These results indicate that gBGC meiotic drive contributes to the spreading of deleterious mutations in human populations. 相似文献
999.
For most Mendelian disorders, targeted genome sequencing is an effective method to detect causative mutations. However, sequencing PCR‐amplified exonic regions and their intronic boundaries can miss large deletions or duplications and mutations that lead to PCR failures in autosomal dominant disorders and in heterozygote detection for X‐linked diseases. Here, a method is described for detecting large (>50 bp) deletions/duplications in the X‐linked α‐galactosidase A (GLA) gene, which cause Fabry disease. Briefly, multiplex PCR mixtures were designed to amplify each GLA exon and an unrelated internal control exon to normalize GLA exonic amplicon peak heights. For each normalized GLA amplicon, the normal control female to male peak‐height ratios were 1.8 to 2.2 (expected 2.0), whereas the expected ratios for deletions or duplications would be ~1.0 or 3.0, respectively. Using this method, three novel deletions, c.369+3_547+954del4096insT, c.194+2049_369+773del2619insCG, and c.207_369+651del814ins231, were detected in unrelated women with signs and/or symptoms suggestive of Fabry disease, but no “sequencing‐detectable” mutations. The deletions were confirmed by sequencing their respective GLA RT‐PCR products. This method can identify gene rearrangements that may be cryptic to genomic DNA sequencing and can be readily adapted to other X‐linked or autosomal dominant genes. Hum Mutat 32:1–8, 2011. © 2011 Wiley‐Liss, Inc. 相似文献
1000.
Kuiper RP Vissers LE Venkatachalam R Bodmer D Hoenselaar E Goossens M Haufe A Kamping E Niessen RC Hogervorst FB Gille JJ Redeker B Tops CM van Gijn ME van den Ouweland AM Rahner N Steinke V Kahl P Holinski-Feder E Morak M Kloor M Stemmler S Betz B Hutter P Bunyan DJ Syngal S Culver JO Graham T Chan TL Nagtegaal ID van Krieken JH Schackert HK Hoogerbrugge N van Kessel AG Ligtenberg MJ 《Human mutation》2011,32(4):407-414