全文获取类型
收费全文 | 153篇 |
免费 | 18篇 |
国内免费 | 18篇 |
专业分类
189篇 |
出版年
2023年 | 5篇 |
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 6篇 |
2015年 | 4篇 |
2014年 | 7篇 |
2013年 | 8篇 |
2012年 | 12篇 |
2011年 | 8篇 |
2010年 | 12篇 |
2009年 | 14篇 |
2008年 | 9篇 |
2007年 | 10篇 |
2006年 | 4篇 |
2005年 | 10篇 |
2004年 | 3篇 |
2003年 | 7篇 |
2002年 | 5篇 |
2001年 | 4篇 |
2000年 | 6篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有189条查询结果,搜索用时 15 毫秒
31.
人TRAIL基因cDNA的克隆及其在COS—7细胞中的表达 总被引:1,自引:0,他引:1
TRAIL(TNFrelatedapoptosisinducingligand)是最近克隆的肿瘤坏死因子(TNF)家族的新成员,由于它的蛋白质结构和生物学效应类似于FAS/APO1L,因此,也被称为APO2L。在低浓度下,TRAIL能迅速地诱导多种肿瘤细胞系的?.. 相似文献
32.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献33.
目的探讨正常SD雌性大鼠性成熟前不同日龄段的脏器与促黄体生成素(LH)、促卵泡素(FSH)、雌二醇(E2)等性激素的变化及其关系。方法从生产群中取出60窝密度状态一致的SD大鼠,在不同日龄随机选取雌性大鼠,检测15、25、32、40日龄时大鼠体重、主要脏器指数,子宫、卵巢组织变化和15、25、32、40、60日龄大鼠血清LH、FSH、E2水平。结果记录了SD雌性大鼠性成熟前各脏器指数和卵巢、子宫组织变化,结果显示大鼠卵巢、子宫的增长速度大于体重的增长,而其他脏器增速大都小于体重的增长。本研究还记录了血清LH、FSH、E2水平在不同日龄段的变化规律,表明血清LH、E2浓度在32日龄时出现较为明显升高。结论不同日龄大鼠脏器指数的动态变化提示大鼠性器官在性发育早期得到机体的优先发育。血清LH、E2水平在32日龄时有了明显升高,提示性腺轴功能已经激活。60日龄大鼠血清性激素水平的波动类似于动情周期的规律性变化,推测大鼠在60日龄前即已进入性成熟,这些结果将为大鼠性发育的相关研究提供重要的参考数据。 相似文献
34.
Heller M von der Ohe M Kleene R Mohajeri MH Schachner M 《Journal of neurochemistry》2003,84(3):557-565
Recognition molecules that carry carbohydrate structures regulate cell interactions during development and play important roles in synaptic plasticity and regeneration in the adult. Glycans appear to be involved in these interactions. We have searched for binding proteins for oligomannosidic structures using the L3 antibody directed against high mannose-type glycans in an anti-idiotypic approach. A selected monoclonal anti-idiotype antibody was used for affinity chromatography and identified basigin as a binding protein from mouse brain detergent lysates. Basigin was found to bind to high mannose-carrying cell recognition molecules, such as myelin-associated glycoprotein, L1, the beta2-subunit of Na+/K+-ATPase and an oligomannosidic neoglycolipid. Furthermore, basigin was involved in outgrowth of astrocytic processes in vitro. A striking homology between the first immunoglobulin (Ig)-like domain of basigin and the fourth Ig-like domain of NCAM, previously shown to bind to oligomannosidic glycans, and the lectin domain of the mannose receptor confirms that basigin is an oligomannose binding lectin. To our knowledge this is the first report that anti-idiotypic antibodies can be used to identify binding partners for carbohydrates. 相似文献
35.
2004—2005年,在内蒙古锡林郭勒盟阿巴嘎旗和东乌珠穆沁旗研究了肝毛细线虫病对黑线毛足鼠种群感染情况,分析肝毛细线虫对黑线毛足鼠的感染率与鼠体年龄以及种群密度的关系。结果表明,黑线毛足鼠达到一定的年龄(或体质量)才可感染肝毛细线虫病,最低感染个体体质量为14.6g。肝毛细线虫对低龄鼠的感染检出率比较低,而对成体鼠感染检出率较高,其感染率和感染度均随着个体年龄的增长而增高(感染率与年龄:r=0.97,P<0.05;感染度与年龄:r=0.93,P<0.05)。此外,黑线毛足鼠体质量与肝毛细线虫感染率和感染度也存在显著的相关关系(感染率与体质量:r=0.99,P<0.05;感染度与体质量:r=0.95,P<0.05),黑线毛足鼠的种群密度则对肝毛细线虫的感染率(r=0.27,P>0.05)和平均感染度(r=0.41,P>0.05)没有明显的影响,其感染率可能与地区不同有关。 相似文献
36.
Molecular evolution of cytochrome c oxidase: rate variation among subunit VIa isoforms 总被引:2,自引:1,他引:2
Schmidt TR; Jaradat SA; Goodman M; Lomax MI; Grossman LI 《Molecular biology and evolution》1997,14(6):595-601
Cytochrome c oxidase (COX) consists of 13 subunits, 3 encoded in the
mitochondrial genome and 10 in the nucleus. Little is known of the role of
the nuclear-encoded subunits, some of which exhibit tissue-specific
isoforms. Subunit VIa is unique in having tissue-specific isoforms in all
mammalian species examined. We examined relative evolutionary rates for the
COX6A heart (H) and liver (L) isoform genes along the length of the
molecule, specifically in relation to the tissue-specific function(s) of
the two isoforms. Nonsynonymous (amino acid replacement) substitutions in
the COX6AH gene occurred more frequently than in the ubiquitously expressed
COX6AL gene. Maximum-parsimony analysis and sequence divergences from
reconstructed ancestral sequences revealed that after the ancestral COX6A
gene duplicated to yield the genes for the H and L isoforms, the sequences
encoding the mitochondrial matrix region of the COX VIa protein experienced
an elevated rate of nonsynonymous substitutions relative to synonymous
substitutions. This is expected for relaxed selective constraints after
gene duplication followed by purifying selection to preserve the
replacements with tissue-specific functions.
相似文献
37.
38.
A modular treatment of molecular traffic through the active site of cholinesterase 总被引:1,自引:0,他引:1 下载免费PDF全文
We present a model for the molecular traffic of ligands, substrates, and products through the active site of cholinesterases (ChEs). First, we describe a common treatment of the diffusion to a buried active site of cationic and neutral species. We then explain the specificity of ChEs for cationic ligands and substrates by introducing two additional components to this common treatment. The first module is a surface trap for cationic species at the entrance to the active-site gorge that operates through local, short-range electrostatic interactions and is independent of ionic strength. The second module is an ionic-strength-dependent steering mechanism generated by long-range electrostatic interactions arising from the overall distribution of charges in ChEs. Our calculations show that diffusion of charged ligands relative to neutral isosteric analogs is enhanced approximately 10-fold by the surface trap, while electrostatic steering contributes only a 1.5- to 2-fold rate enhancement at physiological salt concentration. We model clearance of cationic products from the active-site gorge as analogous to the escape of a particle from a one-dimensional well in the presence of a linear electrostatic potential. We evaluate the potential inside the gorge and provide evidence that while contributing to the steering of cationic species toward the active site, it does not appreciably retard their clearance. This optimal fine-tuning of global and local electrostatic interactions endows ChEs with maximum catalytic efficiency and specificity for a positively charged substrate, while at the same time not hindering clearance of the positively charged products. 相似文献
39.
Carla DB Fernandez Fernanda F Bellentani Glaura SA Fernandes Juliana E Perobelli Ana Paula A Favareto André F Nascimento Antonio C Cicogna Wilma DG Kempinas 《Reproductive biology and endocrinology : RB&E》2011,9(1):32
Background
Obesity is rapidly becoming a worldwide epidemic that affects children and adults. Some studies have shown a relationship between obesity and infertility, but until now it remains controversial. Thus, the aim of the present study was to investigate the effect of high-fat diet-induced obesity on male reproductive parameters. 相似文献40.
Katrin Kuehnle Maria D. Ledesma Lucie Kalvodova Alicia E. Smith Arames Crameri Fabienne Skaanes-Brunner Karin M. Thelen Luka Kulic Dieter Lütjohann Frank L. Heppner Roger M. Nitsch M. Hasan Mohajeri 《Neurochemical research》2009,34(6):1167-1182
Cholesterol is a prominent modulator of the integrity and functional activity of physiological membranes and the most abundant
sterol in the mammalian brain. DHCR24-knock-out mice lack cholesterol and accumulate desmosterol with age. Here we demonstrate
that brain cholesterol deficiency in 3-week-old DHCR24−/− mice was associated with altered membrane composition including disrupted detergent-resistant membrane domain (DRM) structure.
Furthermore, membrane-related functions differed extensively in the brains of these mice, resulting in lower plasmin activity,
decreased β-secretase activity and diminished Aβ generation. Age-dependent accumulation and integration of desmosterol in
brain membranes of 16-week-old DHCR24−/− mice led to the formation of desmosterol-containing DRMs and rescued the observed membrane-related functional deficits. Our
data provide evidence that an alternate sterol, desmosterol, can facilitate processes that are normally cholesterol-dependent
including formation of DRMs from mouse brain extracts, membrane receptor ligand binding and activation, and regulation of
membrane protein proteolytic activity. These data indicate that desmosterol can replace cholesterol in membrane-related functions
in the DHCR24−/− mouse.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
An erratum to this article can be found at 相似文献