首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   421篇
  免费   28篇
  2023年   2篇
  2022年   2篇
  2021年   4篇
  2020年   7篇
  2019年   5篇
  2018年   4篇
  2017年   8篇
  2016年   12篇
  2015年   24篇
  2014年   14篇
  2013年   47篇
  2012年   14篇
  2011年   17篇
  2010年   18篇
  2009年   14篇
  2008年   17篇
  2007年   12篇
  2006年   19篇
  2005年   16篇
  2004年   13篇
  2003年   17篇
  2002年   11篇
  2001年   14篇
  2000年   11篇
  1999年   13篇
  1998年   10篇
  1997年   3篇
  1996年   3篇
  1995年   3篇
  1993年   3篇
  1992年   5篇
  1991年   7篇
  1990年   8篇
  1989年   6篇
  1988年   4篇
  1987年   7篇
  1986年   8篇
  1985年   5篇
  1984年   4篇
  1983年   9篇
  1982年   2篇
  1981年   3篇
  1980年   2篇
  1979年   5篇
  1978年   5篇
  1977年   3篇
  1976年   3篇
  1973年   1篇
  1971年   1篇
  1964年   3篇
排序方式: 共有449条查询结果,搜索用时 328 毫秒
81.
The Tuareg of the Fezzan region (Libya) are characterized by an extremely high frequency (61%) of haplogroup H1, a mitochondrial DNA (mtDNA) haplogroup that is common in all Western European populations. To define how and when H1 spread from Europe to North Africa up to the Central Sahara, in Fezzan, we investigated the complete mitochondrial genomes of eleven Libyan Tuareg belonging to H1. Coalescence time estimates suggest an arrival of the European H1 mtDNAs at about 8,000-9,000 years ago, while phylogenetic analyses reveal three novel H1 branches, termed H1v, H1w and H1x, which appear to be specific for North African populations, but whose frequencies can be extremely different even in relatively close Tuareg villages. Overall, these findings support the scenario of an arrival of haplogroup H1 in North Africa from Iberia at the beginning of the Holocene, as a consequence of the improvement in climate conditions after the Younger Dryas cold snap, followed by in situ formation of local H1 sub-haplogroups. This process of autochthonous differentiation continues in the Libyan Tuareg who, probably due to isolation and recent founder events, are characterized by village-specific maternal mtDNA lineages.  相似文献   
82.
The present investigation recorded significant restoration of seedling growth (root length, shoot length and fresh weight) upon application of 24-epibrassinolide (EBL) and putrescine (Put) to 7-day-old seedlings of Raphanus sativus L. cv. Pusa chetki grown under copper (Cu) ion stress. EBL and Put with/or without Cu ion treated seedlings showed increased titers of ascorbic acid, total phenols and proline when compared with Cu-stressed seedlings. Differential responses in the activities of guaiacol peroxidase (GPOX) and catalase (CAT) were noted for EBL and Put alone or with/or without Cu ion treatment. Decreased activities of glutathione reductase (GR) and superoxide dismutase (SOD) noted for EBL and Put alone were observed to enhance significantly when applied in combination with Cu ion solution. A remarkable decrease in malondialdehyde contents was observed in seedlings treated with EBL and Put alone and with/or without Cu ion stress. Enhanced free radical scavenging activities were also recorded for seedlings given EBL and Put alone or in combination over Cu ion stressed seedlings. Maximum DPPH activity was observed in seedlings treated with Put and EBL 10−9 M + Put. Significant enhancements in deoxyribose and reducing power activities were too recorded for Put, EBL and Put + 10−9 M EBL treatments. Improved seedling growth, antioxidant levels (ascorbic acid, total phenols and proline) and enzymic (GPOX, CAT, SOD and GR) activities and free radical scavenging capacities along with reduced membrane damage in seedlings given EBL and Put with/or without Cu stress suggests significant and positive interactions of EBL and Put in alleviating the Cu ion induced oxidative damage in radish seedlings.  相似文献   
83.
We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route. Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month. After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT. After 1 week, mice were euthanized. Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue. In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC). Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor. Only BM-MSCs (IV > IT) increased the number of M2 macrophages. In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2.  相似文献   
84.
In order to investigate the antiproliferative properties of antamanide, we have synthesized and studied two antamanide analogs where the phenylalanine residue in positions 6 or 9 is substituted by tyrosine, their corresponding linear forms and the cyclic and linear des Phe5,Phe6-Tyr9-analogs. Antamanide and its biologically active synthetic analogs are able to form highly stable complexes with metal ions, particularly Na+, K+ and Ca2+. We studied the ion-binding properties of the Tyr-antamanide analogs by CD and Tb3+ -mediated fluorescence in acetonitrile. In this medium the far-and near-UV CD spectra of the neat Tyr6-antamanide analog are very similar to that of the parent cyclic decapeptide. Substantial differences occur on the contrary in the CD spectra of the neat Tyr9-antamanide, particularly in the regions at 220 nm and 270-290 nm. In acetonitrile, as already found for antamanide, the interaction with the above-mentioned metal ions always produces evident changes in the far- and near-UV CD spectra of both analogs. On the contrary, the CD spectra of the linear deca- and octa- and of the cyclic octa-analogs are affected by the presence of metal ions only in the near-UV region. In the same solvent the Tb3+ -mediated fluorescence spectra of all the synthetic peptides are remarkably affected by the addition of ions. On the basis of the spectral total changes, by using either or both the spectroscopic techniques, it has been possible to determine the ion binding constants for all the linear and cyclic Tyr-antamanide analogs and to compare them with that of the parent peptide. The antitoxic and antiproliferative activities of these antamanide analogs have been tentatively correlated to their ion-binding properties. A preliminary account of this work was given in (1).  相似文献   
85.
We studied object exploration and manipulative behavior in wild‐caught Chimango Caracaras (Milvago chimango), an opportunistic and generalist raptor species, in relation to age and sex differences. Each bird was presented with six objects. We then recorded the latencies to approach and first contact with the objects, the number of objects explored, and the number of exploration events performed on each object. Age influenced the tendency to explore in M. chimango. Compared with adults, juveniles were more likely to explore the objects, approaching and contacting them more quickly. The number of objects explored was also higher in young than adult birds. Both age classes used a variety of manipulative behaviors to explore the objects, some of which have been described as play in others studies. Sex did not affect an individual's likelihood to explore or the number and frequency of manipulative behaviors used during object exploration. The tendency for both young and adult birds to explore and manipulate objects that not resemble prey is likely to be a distinct advantage for a generalist species like M. chimango which must cope with a high diversity of modified environments.  相似文献   
86.
87.
88.
Acid phosphatase (ACP1), adenosine deaminase (ADA), esterase D (ESD), glyoxalase 1 (GLO1), phosphogluconate dehydrogenase (PGD) and phosphoglucomutase 1 and 2 (PGM1 and PGM2) polymorphisms have been studied in the Reggio Calabria province (Southern Italy). The ACP1*A allele and ADA, GLO1, PGD and PGM1 systems have frequencies similar to those reported for Sicily and Southern Italy.  相似文献   
89.

Background

Lysozyme is a widely distributed enzyme present in a variety of tissue and body fluids. Human and hen egg white lysozyme are used as validated model to study protein folding and stability and to understand protein misfolding and aggregation. We recently found that ceftriaxone, a β-lactam antibiotic able to overcome the blood-brain barrier, successfully eliminated the cellular toxic effects of misfolded proteins as Glial Fibrillary Acidic Protein (GFAP) and α-synuclein. To further understand the anti-amyloidogenic properties of ceftriaxone, we studied its activity towards lysozyme aggregation with the aim to investigate a possible chaperone-like activity of this molecule.

Methods

Here we present the results obtained from fluorescence and synchrotron radiation circular dichroism spectroscopies and from molecular docking and molecular dynamics about the lysozyme-ceftriaxone interaction at neutral and acidic pH values.

Results

We found that ceftriaxone exhibits comparable affinity constants to lysozyme in both experimental pH conditions and that its addition enhanced lysozyme stability reducing its aggregation propensity in acidic conditions. Computational methods allowed the identification of the putative binding site of ceftriaxone, thus rationalizing the spectroscopic results.

Conclusions

Spectroscopy data and molecular dynamics indicated a protective effect of ceftriaxone on pathological aggregation phenomena suggesting a chaperone-like effect of this molecule on protein folding.General significanceThese results, in addition to our previous studies on α-synuclein and GFAP, confirm the property of ceftriaxone to inhibit the pathological protein aggregation of lysozyme also by a chaperone-like mechanism, extending the potential therapeutic application of this molecule to some forms of human hereditary systemic amyloidosis.  相似文献   
90.
Despite its evolutionarily conserved function in controlling DNA replication, the chromosomal binding sites of the budding yeast Rif1 protein are not well understood. Here, we analyse genome‐wide binding of budding yeast Rif1 by chromatin immunoprecipitation, during G1 phase and in S phase with replication progressing normally or blocked by hydroxyurea. Rif1 associates strongly with telomeres through interaction with Rap1. By comparing genomic binding of wild‐type Rif1 and truncated Rif1 lacking the Rap1‐interaction domain, we identify hundreds of Rap1‐dependent and Rap1‐independent chromosome interaction sites. Rif1 binds to centromeres, highly transcribed genes and replication origins in a Rap1‐independent manner, associating with both early and late‐initiating origins. Interestingly, Rif1 also binds around activated origins when replication progression is blocked by hydroxyurea, suggesting association with blocked forks. Using nascent DNA labelling and DNA combing techniques, we find that in cells treated with hydroxyurea, yeast Rif1 stabilises recently synthesised DNA. Our results indicate that, in addition to controlling DNA replication initiation, budding yeast Rif1 plays an ongoing role after initiation and controls events at blocked replication forks.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号