全文获取类型
收费全文 | 977篇 |
免费 | 65篇 |
专业分类
1042篇 |
出版年
2023年 | 6篇 |
2022年 | 14篇 |
2021年 | 17篇 |
2020年 | 10篇 |
2019年 | 14篇 |
2018年 | 23篇 |
2017年 | 14篇 |
2016年 | 44篇 |
2015年 | 43篇 |
2014年 | 47篇 |
2013年 | 63篇 |
2012年 | 99篇 |
2011年 | 90篇 |
2010年 | 57篇 |
2009年 | 38篇 |
2008年 | 65篇 |
2007年 | 74篇 |
2006年 | 62篇 |
2005年 | 47篇 |
2004年 | 42篇 |
2003年 | 45篇 |
2002年 | 41篇 |
2001年 | 7篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1997年 | 11篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 7篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有1042条查询结果,搜索用时 15 毫秒
991.
992.
993.
Mariarita Puntoni Federico Bigazzi Laura Sabatino Francesco Sbrana Antonio Musio Beatrice Dal Pino Andrea Ragusa Elena Corsano Tiziana Sampietro 《Biochemical and biophysical research communications》2014
Purpose
Homozygous ABCA1 gene mutation causes Tangier disease (TD). The effects reported in heterozygous state regard plasma HDL, cell cholesterol efflux and coronary artery disease. We investigated whether in vitro replicative skin fibroblast senescence shown in TD proband (Hom), his father (Het), and in a healthy control might be induced in a “gene-dosage way”.Methods
Senescence was evaluated by staining test for β-Galactosidase and telomere length (TL) on fibroblast DNA at different replicative stages. ABCG1 and LDLR (low density lipoprotein receptor) gene expression was also evaluated.Results
Hom cells showed early senescent morphology and reduced growth at all passages in vitro. The cell positive percentage for β-Galactosidase test was highly increased in Hom compared to Het cells at late replicative status (66.1% vs 41.3% respectively). TL was significantly shorter at high stage either in Hom (p < 0.0001) or in Het (p < 0.005). At early replication cycles ABCG1 gene expression was about 3-fold higher in Hom compared to Het cells (0.44 vs 0.14 arbitrary unit).Conclusions
ABCA1 gene mutation may have “gene-dosage way” effect on in vitro fibroblast senescence. Furthermore, increased ABCG1 and LDLR gene expression could highlight a role of ABCA1 on cytoskeleton regulation associated to cell cholesterol metabolism. 相似文献994.
995.
Some neurons of main and external cuneate nuclei are immunoreactive for nitric oxide (NO) synthase, suggesting a role for endogenous NO in the early stages of somatosensory processing. We tested this hypothesis by investigating the possibility that NO modulates cuneate discharge. We observed that both spontaneous and N-methyl-D-aspartate-evoked activities of cuneate neurons were decreased by NO precursor L-arginine. The inhibition of NO synthase, by application of N-nitro-L-arginine methyl ester, instead, abolished the depressant effect induced by L-arginine. Our data suggest a NO modulation of cuneate neurons and provide support for a physiologic role not only in increasing the signal-to-noise ratio in the excited cells but also in a form of surround inhibition. 相似文献
996.
Eberini I Fantucci P Rocco AG Gianazza E Galluccio L Maggioni D Ben ID Galliano M Mazzitello R Gaiji N Beringhelli T 《Proteins》2006,65(3):555-567
Norfloxacin and levofloxacin, two fluoroquinolones of different bulk, rigidity and hydrophobicity taken as model ligands, were docked to one apo and two holo crystallographic structures of bovine beta-lactoglobulin (BLG) using different computational approaches. BLG is a member of the lipocalin superfamily. Lipocalins show a typical b-barrel structure encompassing an internal cavity where small hydrophobic molecules are usually bound. Our studies allowed the identification of two putative binding sites in addition to the calyx. The rigid docking approximation resulted in strong repulsive forces when the ligands were docked into the calyx of the apo form. On the contrary, hindrance was not experienced in flexible docking protocols whether on the apo or on the holo BLG forms, due to allowance for side chain rearrangement. K(i) between 10(-7) and 10(-6) M were estimated for norfloxacin at pH 7.4, smaller than 10(-5) M for levofloxacin. Spectroscopic and electrophoretic techniques experimentally validated the occurrence of an interaction between norfloxacin and BLG. Changes in chemical shift and dynamic parameters were observed between the (19)F NMR spectra of the complex and of the ligand. A K(i) (ca 10(-7) M) comparable with the docking results was estimated through a NMR relaxation titration. Stabilization against unfolding was demonstrated by denaturant gradient gel electrophoresis on the complex versus apo BLG. NMR experimental evidence points to a very loose interaction for ofloxacin, the racemic mixture containing levofloxacin. Furthermore, we were able to calculate in silico K(i)'s comparable to the published experimental values for the complexes of palmitic and retinoic acid with BLG. 相似文献
997.
998.
During programs for the selection of enological yeasts, several hundred natural isolates are usually screened. The scope of these operations is to isolate strains possessing good fermentative properties without necessarily arriving at a precise species designation: in other words, to detect strains belonging to the Saccharomyces sensu stricto complex. In the present study, a pair of primers, designed within the variable D1/D2 region of the 26S subunit of ribosomal yeast RNA, have been constructed. These generate an amplification fragment of 471 bp that is specific for the seven Saccharomyces sensu stricto species, while no signal was obtained for Saccharomyces sensu lato strains (17 species) or for another 18 selected species commonly found in enological environments. A second pair of primers was also constructed, within the 18S rRNA gene, composed of perfectly conserved sequences common for all 42 yeast species examined, which generate a 900 bp (c.) band for all strains. This was used as a positive experimental control in multiplex PCR analysis using all four primers. 相似文献
999.
1000.
Tiziana Angrisano Raffaela Pero Silvia Peluso Simona Keller Silvana Sacchetti Carmelo B Bruni Lorenzo Chiariotti Francesca Lembo 《BMC microbiology》2010,10(1):172