全文获取类型
收费全文 | 82篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 1篇 |
理论与方法论 | 1篇 |
现状及发展 | 10篇 |
研究方法 | 15篇 |
综合类 | 51篇 |
自然研究 | 5篇 |
出版年
2020年 | 1篇 |
2018年 | 2篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 2篇 |
2013年 | 1篇 |
2012年 | 7篇 |
2011年 | 14篇 |
2010年 | 1篇 |
2008年 | 5篇 |
2007年 | 8篇 |
2006年 | 2篇 |
2005年 | 3篇 |
2004年 | 3篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2001年 | 2篇 |
1999年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1979年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有83条查询结果,搜索用时 203 毫秒
51.
52.
Martina Giannaccini Alice Usai Federica Chiellini Viviana Guadagni Massimiliano Andreazzoli Michela Ori Massimo Pasqualetti Luciana Dente Vittoria Raffa 《Cellular and molecular life sciences : CMLS》2018,75(7):1255-1267
Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy. 相似文献
53.
Davis EE Zhang Q Liu Q Diplas BH Davey LM Hartley J Stoetzel C Szymanska K Ramaswami G Logan CV Muzny DM Young AC Wheeler DA Cruz P Morgan M Lewis LR Cherukuri P Maskeri B Hansen NF Mullikin JC Blakesley RW Bouffard GG;NISC Comparative Sequencing Program Gyapay G Rieger S Tönshoff B Kern I Soliman NA Neuhaus TJ Swoboda KJ Kayserili H Gallagher TE Lewis RA Bergmann C Otto EA Saunier S Scambler PJ Beales PL Gleeson JG Maher ER Attié-Bitach T Dollfus H Johnson CA Green ED Gibbs RA Hildebrandt F 《Nature genetics》2011,43(3):189-196
Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to ~5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders. 相似文献
54.
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile 总被引:1,自引:0,他引:1
Kilpeläinen TO Zillikens MC Stančákova A Finucane FM Ried JS Langenberg C Zhang W Beckmann JS Luan J Vandenput L Styrkarsdottir U Zhou Y Smith AV Zhao JH Amin N Vedantam S Shin SY Haritunians T Fu M Feitosa MF Kumari M Halldorsson BV Tikkanen E Mangino M Hayward C Song C Arnold AM Aulchenko YS Oostra BA Campbell H Cupples LA Davis KE Döring A Eiriksdottir G Estrada K Fernández-Real JM Garcia M Gieger C Glazer NL Guiducci C Hofman A Humphries SE Isomaa B Jacobs LC Jula A Karasik D Karlsson MK 《Nature genetics》2011,43(8):753-760
Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ~2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance. 相似文献
55.
56.
The only remaining self-sustaining native population of lacustrine Lahontan cutthroat trout ( Oncorhynchus clarki henshawi ) not affected by nonnative salmonids is in Summit Lake, Humboldt County, Nevada. Annual spawning runs in 1993 and 1994 were monitored at a fish trap on Mahogany Creek, the only spawning tributary for Summit Lake. Number of spawners was similar in both years, with 1290 upstream migrants observed in 1993 and 1255 in 1994. In 1993, 137 postspawners (10.6% of upstream migrants) returned to the lake, and in 1994, 434 postspawners (34.6% of upstream migrants) returned downstream through the fish trap. Two distinct groups of subadult Lahontan cutthroat trout were observed moving downstream in 1994. The first group passed downstream between 27 April and 29 July and included 1188 fish (average fork length = 90 mm). Between 1 August and 31 October, 1160 fish (average fork length = 42 mm) moved downstream. Size differences of these 2 groups suggest that the 1st group comprised fish that had overwintered in Mahogany Creek, while the 2nd group were probably young-of-the-year. 相似文献
57.
58.
This paper reports on an action research study for the development of a common program on inspection and accreditation of blood collection establishments in the European Union member states. Using soft systems methodology to guide the study, we have developed the systems required and arrived at the actions that are necessary to realize and maintain them. 相似文献
59.
Promoters are in the operators in phage lambda 总被引:13,自引:0,他引:13
60.
Sequence of a repressor-binding site in the DNA of bacteriophage lamda 总被引:31,自引:0,他引:31