全文获取类型
收费全文 | 4933篇 |
免费 | 348篇 |
国内免费 | 1篇 |
专业分类
5282篇 |
出版年
2023年 | 30篇 |
2022年 | 69篇 |
2021年 | 143篇 |
2020年 | 73篇 |
2019年 | 104篇 |
2018年 | 158篇 |
2017年 | 114篇 |
2016年 | 164篇 |
2015年 | 254篇 |
2014年 | 311篇 |
2013年 | 384篇 |
2012年 | 462篇 |
2011年 | 423篇 |
2010年 | 259篇 |
2009年 | 202篇 |
2008年 | 280篇 |
2007年 | 294篇 |
2006年 | 241篇 |
2005年 | 225篇 |
2004年 | 208篇 |
2003年 | 161篇 |
2002年 | 136篇 |
2001年 | 42篇 |
2000年 | 53篇 |
1999年 | 48篇 |
1998年 | 26篇 |
1997年 | 29篇 |
1996年 | 18篇 |
1995年 | 24篇 |
1994年 | 20篇 |
1993年 | 24篇 |
1992年 | 29篇 |
1991年 | 25篇 |
1990年 | 17篇 |
1989年 | 22篇 |
1988年 | 12篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 17篇 |
1984年 | 11篇 |
1983年 | 15篇 |
1982年 | 12篇 |
1981年 | 10篇 |
1979年 | 14篇 |
1978年 | 10篇 |
1977年 | 12篇 |
1975年 | 7篇 |
1974年 | 9篇 |
1973年 | 14篇 |
1968年 | 7篇 |
排序方式: 共有5282条查询结果,搜索用时 7 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.
Lorenzo Dal Bo Paolo Mazzucchelli Antonio Marzo 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2000,749(2):258
Zofenopril is a pro-drug designed to undergo metabolic hydrolysis yielding the active free sulfhydryl compound zofenoprilat, which is an angiotensin converting enzyme (ACE) inhibitor, endowed also with a marked cardioprotective activity. A simple, highly sensitive specific LC–MS–MS method was developed for the determination of zofenopril and zofenoprilat in human plasma. In order to prevent oxidative degradation of zofenoprilat and its internal standard, their free sulfhydryl groups were protected by treatment with N-ethylmaleimide (NEM), which produced the succinimide derivatives. The compounds and their corresponding fluorine derivatives, used as internal standards, were extracted from plasma with toluene. The reconstituted dried extracts were chromatographed and then monitored by a triple-stage-quadrupole instrument operating in the negative ion spray ionization mode. The method was validated over the concentration range of 1–300 ng/ml for zofenopril and 2–600 ng/ml for zofenoprilat. Inter- and intra-assay precision and accuracy of both zofenopril and zofenoprilat were better than 10%. The limit of quantitation was 1 ng/ml with zofenopril and 2 ng/ml with zofenoprilat. Extraction recovery proved to be on average 84.8% with zofenopril and 70.1% with zofenoprilat. Similar recoveries were shown by the above two internal standards. The method was applied to measure plasma concentrations of zofenopril and zofenoprilat in 18 healthy volunteers treated orally with zofenopril calcium salt at the dose of 60 mg. 相似文献
5.
C A Kappel M C Dal Canto R W Melvold B S Kim 《Journal of immunology (Baltimore, Md. : 1950)》1991,147(12):4322-4326
Intracerebral inoculation of susceptible mice with Theiler's murine encephalomyelitis virus induces a demyelinating disease that is similar to human multiple sclerosis. This murine model for human multiple sclerosis is apparently immune-mediated and the genes involved in the immune response influence the outcome of disease susceptibility as observed with human multiple sclerosis. These genes include the MHC and TCR genes. However, the functional relationships among these genes on the disease susceptibility has not yet been studied. In this study, we demonstrate that the effect of the H-2s genotype from susceptible SJL/J mice overrides the resistant effect of the BALB/c TCR beta-chain gene in CXJ recombinant-inbred and BALB.S congenic mice. These results strongly suggest the presence of a hierarchy of genes involved in the immune response in Theiler's murine encephalomyelitis virus-induced demyelinating disease. 相似文献
6.
7.
8.
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
9.
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