全文获取类型
收费全文 | 4188篇 |
免费 | 286篇 |
国内免费 | 1篇 |
出版年
2023年 | 26篇 |
2022年 | 60篇 |
2021年 | 129篇 |
2020年 | 63篇 |
2019年 | 84篇 |
2018年 | 135篇 |
2017年 | 99篇 |
2016年 | 142篇 |
2015年 | 226篇 |
2014年 | 271篇 |
2013年 | 348篇 |
2012年 | 403篇 |
2011年 | 361篇 |
2010年 | 224篇 |
2009年 | 185篇 |
2008年 | 241篇 |
2007年 | 259篇 |
2006年 | 211篇 |
2005年 | 184篇 |
2004年 | 175篇 |
2003年 | 137篇 |
2002年 | 115篇 |
2001年 | 25篇 |
2000年 | 24篇 |
1999年 | 33篇 |
1998年 | 19篇 |
1997年 | 18篇 |
1996年 | 12篇 |
1995年 | 21篇 |
1994年 | 13篇 |
1993年 | 21篇 |
1992年 | 17篇 |
1991年 | 13篇 |
1990年 | 10篇 |
1989年 | 16篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 17篇 |
1984年 | 8篇 |
1983年 | 11篇 |
1982年 | 6篇 |
1981年 | 8篇 |
1980年 | 6篇 |
1979年 | 10篇 |
1978年 | 9篇 |
1977年 | 8篇 |
1975年 | 6篇 |
1974年 | 7篇 |
1973年 | 12篇 |
排序方式: 共有4475条查询结果,搜索用时 31 毫秒
1.
Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of genetic diseases characterized by a primary defect in insulin secretion and hyperglycemia, non-ketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of auto-antibodies. It accounts for 2–5% of all cases of non-type 1 diabetes. MODY subtype 2 is caused by mutations in the glucokinase (GCK) gene. In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). Based on these results, we have developed a specific PCR-RFLP assay to detect this mutation and tested 122 related volunteers from the same family. This mutation in the GCK gene was detected in 21 additional subjects who also had the clinical features of this genetic disease. In conclusion, we identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene. We also developed a specific assay that is fast, cheap and reliable to detect this mutation. Finally, we built a molecular ancestry model based on our results for the migration of individuals carrying this genetic mutation from Northern Italy to Brazil. 相似文献
2.
Sashko Spassov Dietmar Pfeifer Karl Strosing Stefan Ryter Matthias Hummel Simone Faller Alexander Hoetzel 《PloS one》2014,9(7)
Recently, we have shown that inhalation of hydrogen sulfide (H2S) protects against ventilator-induced lung injury (VILI). In the present study, we aimed to determine the underlying molecular mechanisms of H2S-dependent lung protection by analyzing gene expression profiles in mice. C57BL/6 mice were subjected to spontaneous breathing or mechanical ventilation in the absence or presence of H2S (80 parts per million). Gene expression profiles were determined by microarray, sqRT-PCR and Western Blot analyses. The association of Atf3 in protection against VILI was confirmed with a Vivo-Morpholino knockout model. Mechanical ventilation caused a significant lung inflammation and damage that was prevented in the presence of H2S. Mechanical ventilation favoured the expression of genes involved in inflammation, leukocyte activation and chemotaxis. In contrast, ventilation with H2S activated genes involved in extracellular matrix remodelling, angiogenesis, inhibition of apoptosis, and inflammation. Amongst others, H2S administration induced Atf3, an anti-inflammatory and anti-apoptotic regulator. Morpholino mediated reduction of Atf3 resulted in elevated lung injury despite the presence of H2S. In conclusion, lung protection by H2S during mechanical ventilation is associated with down-regulation of genes related to oxidative stress and inflammation and up-regulation of anti-apoptotic and anti-inflammatory genes. Here we show that Atf3 is clearly involved in H2S mediated protection. 相似文献
3.
4.
5.
6.
7.
8.
Cristina Cereda Emanuela Leoni Pamela Milani Orietta Pansarasa Giuliano Mazzini Stefania Guareschi Elena Alvisi Andrea Ghiroldi Luca Diamanti Stefano Bernuzzi Mauro Ceroni Emanuela Cova 《PloS one》2013,8(10)
Several lines of evidence support the hypothesis of a toxic role played by wild type SOD1 (WT-SOD1) in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). In this study we investigated both distribution and expression profile of WT-SOD1 in leukocytes from 19 SALS patients and 17 healthy individuals. Immunofluorescence experiments by confocal microscopy showed that SOD1 accumulates in the nuclear compartment in a group of SALS subjects. These results were also confirmed by western blot carried out on soluble nuclear and cytoplasmic fractions, with increased nuclear SOD1 level (p<0.05). In addition, we observed the presence of cytoplasmic SOD1 aggregates in agreement with an increased amount of the protein recovered by the insoluble fraction. A further confirmation of the overall increased level of SOD1 has been obtained from single cells analysis using flow cytometry as cells from SALS patients showed an higher SOD1 protein content (p<0.05). These findings add further evidence to the hypothesis of an altered WT-SOD1 expression profile in peripheral blood mononuclear cells (PBMCs) from patients with ALS suggesting that WT-SOD1 species with different degrees of solubility could be involved in the pathogenesis of the disease. 相似文献
9.
Duccio Malinverni Simone Marsili Alessandro Barducci Paolo De Los Rios 《PLoS computational biology》2015,11(6)
Hsp70s are a class of ubiquitous and highly conserved molecular chaperones playing a central role in the regulation of proteostasis in the cell. Hsp70s assist a myriad of cellular processes by binding unfolded or misfolded substrates during a complex biochemical cycle involving large-scale structural rearrangements. Here we show that an analysis of coevolution at the residue level fully captures the characteristic large-scale conformational transitions of this protein family, and predicts an evolutionary conserved–and thus functional–homo-dimeric arrangement. Furthermore, we highlight that the features encoding the Hsp70 dimer are more conserved in bacterial than in eukaryotic sequences, suggesting that the known Hsp70/Hsp110 hetero-dimer is a eukaryotic specialization built on a pre-existing template. 相似文献
10.
Pollens from Pinus canariensis, P. nigra, P. pinaster, P. pinea, Castanea sativa, Magnolia grandiflora, Olea sativa cv frantoio, cv itrana, cv pisciottana were examined for their free amino acid composition. A large amount of proline was found in all species; pollens of Olea also contain a large amount of serine. 相似文献