全文获取类型
收费全文 | 194篇 |
免费 | 17篇 |
专业分类
211篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 6篇 |
2015年 | 12篇 |
2014年 | 6篇 |
2013年 | 10篇 |
2012年 | 17篇 |
2011年 | 14篇 |
2010年 | 10篇 |
2009年 | 6篇 |
2008年 | 14篇 |
2007年 | 17篇 |
2006年 | 15篇 |
2005年 | 10篇 |
2004年 | 7篇 |
2003年 | 12篇 |
2002年 | 9篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1986年 | 3篇 |
1980年 | 1篇 |
排序方式: 共有211条查询结果,搜索用时 15 毫秒
41.
Ahlqvist KJ Hämäläinen RH Yatsuga S Uutela M Terzioglu M Götz A Forsström S Salven P Angers-Loustau A Kopra OH Tyynismaa H Larsson NG Wartiovaara K Prolla T Trifunovic A Suomalainen A 《Cell metabolism》2012,15(1):100-109
Somatic stem cell (SSC) dysfunction is typical for different progeroid phenotypes in mice with genomic DNA repair defects. MtDNA mutagenesis in mice with defective Polg exonuclease activity also leads to progeroid symptoms, by an unknown mechanism. We found that Polg-Mutator mice had neural (NSC) and hematopoietic progenitor (HPC) dysfunction already from embryogenesis. NSC self-renewal was decreased in vitro, and quiescent NSC amounts were reduced in vivo. HPCs showed abnormal lineage differentiation leading to anemia and lymphopenia. N-acetyl-L-cysteine treatment rescued both NSC and HPC abnormalities, suggesting that subtle ROS/redox changes, induced by mtDNA mutagenesis, modulate SSC function. Our results show that mtDNA mutagenesis affected SSC function early but manifested as respiratory chain deficiency in nondividing tissues in old age. Deletor mice, having mtDNA deletions in postmitotic cells and no progeria, had normal SSCs. We propose that SSC compartment is sensitive to mtDNA mutagenesis, and that mitochondrial dysfunction in SSCs can underlie progeroid manifestations. 相似文献
42.
Lee-Rueckert M Vikstedt R Metso J Ehnholm C Kovanen PT Jauhiainen M 《Journal of lipid research》2006,47(8):1725-1732
In vitro experiments have demonstrated that exogenous phospholipid transfer protein (PLTP), i.e. purified PLTP added to macrophage cultures, influences ABCA1-mediated cholesterol efflux from macrophages to HDL. To investigate whether PLTP produced by the macrophages (i.e., endogenous PLTP) is also part of this process, we used peritoneal macrophages derived from PLTP-knockout (KO) and wild-type (WT) mice. The macrophages were transformed to foam cells by cholesterol loading, and this resulted in the upregulation of ABCA1. Such macrophage foam cells from PLTP-KO mice released less cholesterol to lipid-free apolipoprotein A-I (apoA-I) and to HDL than did the corresponding WT foam cells. Also, when plasma from either WT or PLTP-KO mice was used as an acceptor, cholesterol efflux from PLTP-KO foam cells was less efficient than that from WT foam cells. After cAMP treatment, which upregulated the expression of ABCA1, cholesterol efflux from PLTP-KO foam cells to apoA-I increased markedly and reached a level similar to that observed in cAMP-treated WT foam cells, restoring the decreased cholesterol efflux associated with PLTP deficiency. These results indicate that endogenous PLTP produced by macrophages contributes to the optimal function of the ABCA1-mediated cholesterol efflux-promoting machinery in these cells. Whether macrophage PLTP acts at the plasma membrane or intracellularly or shuttles between these compartments needs further study. 相似文献
43.
Antti Nyyssölä Ville Pihlajaniemi Riikka Järvinen Saara Mikander Hanna Kontkanen Kristiina Kruus Heikki Kallio Johanna Buchert 《Enzyme and microbial technology》2013,52(4-5):272-278
Isolates from gardening waste compost and 38 culture collection microbes were grown on agar plates at pH 4.0 with the cutinase model substrate polycaprolactone as a carbon source. The strains showing polycaprolactone hydrolysis were cultivated in liquid at acidic pH and the cultivations were monitored by assaying the p-nitrophenyl butyrate esterase activities. Culture supernatants of four strains were analyzed for the hydrolysis of tritiated apple cutin at different pHs. Highest amounts of radioactive hydrolysis products were detected at pHs below 5. The hydrolysis of apple cutin by the culture supernatants at acidic pH was further confirmed by GC–MS analysis of the hydrolysis products. On the basis of screening, the acidic cutinase from Aspergillus niger CBS 513.88 was chosen for heterogeneous production in Pichia pastoris and for analysis of the effects of pH on activity and stability. The recombinant enzyme showed activity over a broad range of pHs with maximal activity between pH 5.0 and 6.5. Activity could be detected still at pH 3.5. 相似文献
44.
Demographic history has influenced nucleotide diversity in European Pinus sylvestris populations 总被引:1,自引:0,他引:1
Pyhäjärvi T García-Gil MR Knürr T Mikkonen M Wachowiak W Savolainen O 《Genetics》2007,177(3):1713-1724
To infer the role of natural selection in shaping standing genetic diversity, it is necessary to assess the genomewide impact of demographic history on nucleotide diversity. In this study we analyzed sequence diversity of 16 nuclear loci in eight Pinus sylvestris populations. Populations were divided into four geographical groups on the basis of their current location and the geographical history of the region: northern Europe, central Europe, Spain, and Turkey. There were no among-group differences in the level of silent nucleotide diversity, which was approximately 0.005/bp in all groups. There was some evidence that linkage disequilibrium extended further in northern Europe than in central Europe: the estimates of the population recombination rate parameter, rho, were 0.0064 and 0.0294, respectively. The summary statistics of nucleotide diversity in central and northern European populations were compatible with an ancient bottleneck rather than the standard neutral model. 相似文献
45.
The present study was aimed to localise lymphatic vessels and their growth factors in human and mouse skeletal muscle with
immunohistochemistry and specific antibodies (VEGFR-3, LYVE-1, VEGF-C and VEGF-D). The largest lymphatic vessels were found
in perimysial connective tissue next to the arteries and veins, as has been shown earlier with electron microscopy. As a new
finding, we also found small LYVE-1 positive vessels in the capillary bed between muscle fibres. These vessels were located
next to CD31 positive blood capillaries and were of the same size, but fewer in number. In addition, we described the localisation
of the two main lymphangiogenic growth factor proteins, vascular endothelial growth factor-C and -D. Both proteins were expressed
in skeletal muscle at mRNA and protein levels. VEGF-D was located under the sarcolemma in some of the muscle fibres, in the
endothelia of larger blood vessels and in fibroblasts. VEGF-C protein was localised to the nerves and muscle spindles, to
fibroblasts and surrounding connective tissue, but was not found in muscle fibres or endothelial cells. Our results are the
first to suggest the presence of lymphatic capillaries throughout the skeletal muscle, and to present the localisation of
VEGF-C and -D in the muscles.
Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at . 相似文献
46.
Viiri LE Raitakari OT Huhtala H Kähönen M Rontu R Juonala M Hutri-Kähönen N Marniemi J Viikari JS Karhunen PJ Lehtimäki T 《Journal of lipid research》2006,47(6):1298-1306
The common apolipoprotein E (apoE) gene (APOE) epsilon2/epsilon3/epsilon4 polymorphism explains part of serum lipid variation, and polymorphisms in the APOE promoter region have been proposed to participate in the regulation of serum lipid levels within the most common APOE epsilon3/epsilon3 genotype group. We determined APOE -219G/T and +113G/C promoter genotypes and estimated APOE haplotypes in 525 participants of the Cardiovascular Risk in Young Finns Study. We studied the associations of the APOE promoter polymorphisms and their haplotypes with cross-sectional and longitudinal serum lipid and apolipoprotein concentrations as well as with flow-mediated dilatation (FMD), carotid artery compliance (CAC), and intima-media thickness (IMT) within the APOE epsilon3/epsilon3 carriers. We found no significant association between the APOE promoter genotypes and serum lipids [low density lipoprotein-cholesterol (LDL-C), HDL-C, and triglycerides], apolipoproteins (apoA-I and apoB), or brachial artery FMD, CAC, or carotid IMT in either men or women. In longitudinal analyses in males, the carriers of heterozygous genotypes (-219G/T or +113G/C) and, furthermore, carriers of the -219T/+113C/epsilon3 haplotype had significantly higher LDL-C and total cholesterol concentrations throughout the 21 year follow-up period compared with homozygous G allele carriers or noncarriers of the -219T/+113C/epsilon3 haplotype. Such associations were not found in females. In summary, the APOE promoter polymorphisms -219G/T and +113G/C as well as their haplotype are associated with longitudinal changes in LDL-C and total cholesterol concentrations in young Finnish males but do not seem to be major determinants for FMD, CAC, or carotid IMT in males or females. 相似文献
47.
Background
We have previously shown that ultraviolet-A (UVA) radiation enhances metastatic lung colonization capacity of B16-F1 melanoma cells. The aim of this study was to examine changes in expression profile of genes in mouse melanoma B16-F1 cells exposed to UVA radiation. 相似文献48.
49.
50.
Seppo Rytkönen Laura Kvist Riikka Mikkonen Markku Orell 《Journal of avian biology》2007,38(3):273-277
We asked whether willow tit Parus montanus males adjust their parental care according to their paternity in current brood. The origin of the nestlings was determined by using molecular technique, and the studied broods were assigned into extra-pair paternity (EPP) broods, if at least one nestling was fathered by another male, and truly monogamous broods. Over 3 years, 14 of 40 broods (35%) included EP-offspring, and 29 of 273 nestlings (11%) were EP-young. Intensity of parental care was measured with risk-taking against a potential predator, mounted stoat Mustela erminea . The results showed that risk-taking by EPP males did not differ from that by monogamous males. Neither was the sexual difference in risk-taking different at EPP and monogamous broods. Our results are consistent with the hypothesis that males do not adjust their level of care to paternity, perhaps because they have no reliable cues for assessing their paternity. This may be related to the success of mate-guarding in their breeding environment, closed forests. Guarding is seemingly successful as the EPP levels are rather low, but it is not totally sure making the potential costs, rejection of own young, too high. We also discuss other population characteristics which may further prevent the evolution of paternity assessment in northern willow tits. 相似文献