全文获取类型
收费全文 | 807篇 |
免费 | 106篇 |
国内免费 | 26篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 2篇 |
妇产科学 | 4篇 |
基础医学 | 227篇 |
口腔科学 | 9篇 |
临床医学 | 67篇 |
内科学 | 133篇 |
皮肤病学 | 3篇 |
神经病学 | 76篇 |
特种医学 | 7篇 |
外科学 | 14篇 |
综合类 | 113篇 |
预防医学 | 57篇 |
眼科学 | 7篇 |
药学 | 143篇 |
中国医学 | 50篇 |
肿瘤学 | 24篇 |
出版年
2024年 | 6篇 |
2023年 | 14篇 |
2022年 | 20篇 |
2021年 | 38篇 |
2020年 | 35篇 |
2019年 | 42篇 |
2018年 | 23篇 |
2017年 | 27篇 |
2016年 | 24篇 |
2015年 | 36篇 |
2014年 | 38篇 |
2013年 | 68篇 |
2012年 | 60篇 |
2011年 | 72篇 |
2010年 | 45篇 |
2009年 | 38篇 |
2008年 | 39篇 |
2007年 | 34篇 |
2006年 | 37篇 |
2005年 | 32篇 |
2004年 | 25篇 |
2003年 | 24篇 |
2002年 | 17篇 |
2001年 | 13篇 |
2000年 | 13篇 |
1999年 | 7篇 |
1998年 | 11篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 10篇 |
1989年 | 4篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 8篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1973年 | 1篇 |
排序方式: 共有939条查询结果,搜索用时 171 毫秒
1.
J.K. MOHANA RAO 《Chemical biology & drug design》1987,29(2):276-281
Based on residue characteristic physical parameters, a new scoring matrix, called EMPAR, for amino acid exchanges in proteins was obtained. When comparing protein sequences for detecting homologies, the use of this matrix in place of the Dayhoff log-odds matrix yields results that reflect the topological similarities in the proteins. The use of EMPAR is equivalent to the parametric correlation coefficient approach of Ooi and his colleagues. This matrix correlates at 0.63 with the Dayhoff matrix. 相似文献
2.
With the method of rapid gel sequencing, the complete nueleotide sequence of Fasciolopsis buski 5S rRNA has been determined: AAC GGG AUG AAG CUA GAC AUG UGG CGG CCU AGU UGG AGG UCG GAA CUC GGA AGU UAA GGA AUG UUG GGC CUG GUU AGU ACU GGU AUG GGU GAC CUU GGG AAU ACC GGG UGU UGC GUC CA_(OH) This have been compared with 553 species of other organisms 5S rRNA sequences previously published and fitted to a secondary structural model. 相似文献
3.
PTEN与基质金属蛋白酶在胃癌组织中的表达及意义 总被引:8,自引:3,他引:5
目的:探讨PTEN与基质金属蛋白酶(MMP)在胃癌组织中的表达、相互关系及意义。方法:应用免疫组化SP技术检测80例胃癌组织中PTEN、MMP2和MMP9表达,同时检测20例正常对照组胃粘膜中PTEN表达。结果:胃癌组织中PTEN高表达率35/80(43.8%)显著低于对照组20/20(100. 0%)(P<0.01);PTEN表达与胃癌分化程度、浸润深度、淋巴结转移和肿瘤分期显著相关;胃癌组织中 MMP2、MMP9阳性表达率分别为41/80(51.3%)、29/80(36.3%),与胃癌浸润深度、淋巴结转移和肿瘤分期显著相关;PTEN与MMP2、MMP9表达显著负相关,与病人预后相关,Kaplan-Meier生存曲线分析显示PTEN高表达者术后累计生存率显著高于低表达者,PTEN高表达者术后3年、5年生存率显著高于低表达者;MMP2、MMP9阳性表达者术后累计生存率显著低于阴性表达者,MMP2、MMP9阳性表达者术后3年、5年生存率显著低于阴性表达者。结论:胃癌组织中PTEN表达显著减少,PTEN 与MMP2、MMP9表达显著负相关,PTEN可能通过调控胃癌组织MMP2、MMP9表达,抑制胃癌的浸润和转移,影响病人的预后。 相似文献
4.
5.
TCR repertoire in early fetal mouse thymus 总被引:1,自引:0,他引:1
Ohki-Hamazaki Hiroko; Makino Yasuhiko; Kanno Masamoto; Koseki Haruhiko; Akasaka Takeshi; Taniguchi Masaru 《International immunology》1995,7(3):493-499
We investigated the rearrangement and expression of TCR genesin mouse fetal thymus organ culture, a system that avoids subsequententry of hematopoietic precursor cells. The first observablerearranged TCR gene was homogeneous V2-J2, detectable as earlyas fetal day 11 (d11) in the thymic primordla. The productiveTCR was homogeneous V5-J1, first detectable in d13 thymocytes,followed by adult-type TCR (V4 and V7). Sequence analysis ofTCR revealed five types of V-J junctional sequences. In thevery early stage, a homogeneous V-J junction is generated viaa short homology sequence in the coding region (Type I), whilea short homology sequence in the P-nucleotlde rather than thecoding region is used in the following stage (Type II). In thelater embryonic stages, diverse V-J junctions are generatedby well-known mechanisms, such as P-nucleotide (Type III), N-regioninsertion (Type IV) or trimming of the coding ends (Type V).These findings suggest that the generation of homogeneous TCR (V2 and V5) in the early fetal stages is due to the intrinsicrearrangement mechanisms and is in stage specific manner. 相似文献
6.
《European journal of medical genetics》2022,65(10):104595
BackgroundPathogenic variants in the transmembrane sulfate transporter protein SLC26A2 are associated with different phenotypes of inherited chondrodysplasias. As limited data is published from India, in this study we sought to elucidate the molecular basis of inherited chondrodysplasias in an Indian cohort.MethodsMolecular screening of 32 fetuses with antenatally diagnosed lethal skeletal dysplasia was performed by next generation sequencing and Sanger sequencing. The genotype-protein phenotype characterization was done using computational biology techniques like homology modelling, stability and pathogenicity predictions.ResultsWe identified five rare autosomal recessive SLC26A2 [NM_000112.4] variants, including three homozygous c.796dupA(p.Thr266Asnfs*12), c.1724delA(p.Lys575Serfs*10), and c.1375_1377dup(p.Val459dup) and two heterozygous variants (c.532C > T(p.Arg178*)) and (c.1382C > T(p.Ala461Val)) in compound heterozygous form in a total of four foetuses. Genotype-protein phenotype annotations highlighted that the clinically severe achondrogenesis 1B causative c.796dupA(p.Thr266Asnfs*12) and c.1724delA(p.Lys575Serfs*10)variants impact SLC26A2 protein structure by deletion of the protein core and transmembrane STAS domains, respectively. In clinically moderate atelosteogenesis type 2 phenotype, the c.1382C > T(p.Ala461Val) variant is predicted to distort alpha helix conformation and alter the bonding properties and free energy dynamics of transmembrane domains and the c.532C > T(p.Arg178*) variant results in loss of both core transmembrane and STAS domains of the SLC26A2 protein. The c.1375_1377dup(p.Val459dup) variant identified in clinically milder atelosteogenesis type II-diastrophic dysplasia spectrum lethal phenotype is predicted to decrease the Qualitative Model Energy Analysis (QMean), which affects major geometrical aspects of the SLC26A2 protein structure.ConclusionWe expand the spectrum of SLC26A2 related lethal chondrodysplasia and report three novel variants correlating clinical severity and protein phenotype within the lethal spectrum of this rare dysplasia. We demonstrate the relevance of structural characterization to aid novel variant reclassification to provide better prenatal management and reproductive options to families with lethal antenatal skeletal disorder. 相似文献
7.
Molecular identification of a novel human rotavirus in relation to subgroup and electropherotype of genomic RNA 总被引:3,自引:0,他引:3
O Nakagomi H Oyamada S Kuroki Y Kobayashi A Ohshima T Nakagomi 《Journal of medical virology》1989,28(3):163-168
A total of 41 stool rotavirus specimens collected from children with acute diarrhea at four different locations in Akita Prefecture, Japan, during the peak of the winter diarrhea epidemic in 1988 were analyzed by polyacrylamide gel electrophoresis of viral RNA in conjunction with subgrouping assay. We found that a single strain predominated, with cocirculating strains with less common electropherotypes at a given location, and that two different strains could predominate at geographically close but different locations even during a very limited time of the epidemic season. Furthermore, we isolated a human rotavirus strain (AU125) that was similar to the AU-1 strain in that it possessed a long RNA pattern yet belonged to subgroup I. Genetic analysis by RNA-RNA hybridization assay indicated that the AU125 strain was distinct from two previously identified human rotavirus gene groups (genogroups) represented by the Wa strain (subgroup II with long RNA electropherotype) and the DS-1 strain (subgroup I with short RNA electropherotype), but was very closely related to the AU-1 strain. These data suggest that the genetic diversity of human rotaviruses may be more extensive than was previously thought. 相似文献
8.
Yoshinobu Uno Chizuko Nishida Yuki Oshima Satoshi Yokoyama Ikuo Miura Yoichi Matsuda Masahisa Nakamura 《Chromosome research》2008,16(4):637-647
There are regional variations of sex chromosome morphologies in the Japanese wrinkled frog, Rana rugosa (2n = 26): heterogametic ZZ/ZW-type and XX/XY-type sex chromosomes, and two different types of homomorphic sex chromosomes. To search for homology between the ZW and XY sex chromosomes and the chromosome rearrangements that have occurred during sex chromosomal differentiation in R. rugosa, we performed chromosome mapping of sexual differentiation genes for R. rugosa by FISH. Three genes, AR, SF-1/Ad4BP and Sox3, were localized to both the ZW and XY chromosomes, and their locations were all different between the Z and W and between the X and Y. AR and SF-1/Ad4BP were located on the short arms of the W and X and the long arms of Z and Y, and Sox3 was mapped to the different locations on the long arms between the Z and W and between the X and Y, probably as a result of multiple rearrangements that occurred during the process of sex chromosome differentiation. However, the chromosomal locations of three genes were almost consistent between the Z and Y and between the W and X, indicating that the Z and Y chromosomes and the W and X chromosomes were respectively derived from the same origins. Dmrt1, which is located on avian sex chromosomes, was localized to autosomes in R. rugosa with both the ZW and XY sex chromosomes, suggesting that Dmrt1 might not be related to sex determination in this species. 相似文献
9.
10.
目的构建人第10号染色体上磷酸酶和张力蛋白同源缺失的基因(phosphatase and tensin homology deleted on chromosome ten,PTEN)原核表达质粒,使其在原核细胞中高效表达并进行纯化。方法将全长片段插入原核表达载体pGEX-4T-1,构建重组子pGEX-4T-1-PTEN,转化BL-21感受态细胞。经异丙基硫代-β-D-半乳糖苷(IPTG)诱导表达PTEN融合蛋白的可诱导性表达,通过SDS-PAGE电泳、Western印迹分析证实蛋白表达的特异性。并用谷胱甘肽-S-转移酶(glutathione-Stransferase,GST)亲和层析对融合蛋白进行纯化。结果成功构建了原核表达载体pGEX-4T-1-PTEN,并将PTEN融合蛋白的成功表达,通过SDS-PAGE电泳、Western印迹分析,证实了蛋白表达的特异性。并对蛋白进行了纯化,获得了GST-PTEN融合蛋白的纯品。结论成功表达、纯化了GST-PTEN融合蛋白,为进一步研究PTEN蛋白的功能及其与其它功能性蛋白的相互作用研究奠定了基础。 相似文献