全文获取类型
收费全文 | 252篇 |
免费 | 22篇 |
专业分类
274篇 |
出版年
2022年 | 2篇 |
2021年 | 3篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 5篇 |
2016年 | 3篇 |
2015年 | 11篇 |
2014年 | 16篇 |
2013年 | 21篇 |
2012年 | 19篇 |
2011年 | 10篇 |
2010年 | 8篇 |
2009年 | 14篇 |
2008年 | 11篇 |
2007年 | 10篇 |
2006年 | 12篇 |
2005年 | 8篇 |
2004年 | 8篇 |
2003年 | 5篇 |
2002年 | 3篇 |
2001年 | 11篇 |
2000年 | 11篇 |
1999年 | 4篇 |
1998年 | 11篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有274条查询结果,搜索用时 0 毫秒
251.
A new simple, rapid and sensitive reversed‐phase liquid chromatographic method was developed and validated for the simultaneous determination of methocarbamol (MET) and aspirin (ASP) in their combined dosage form. The separation of these compounds was achieved within 6.0 min on a CLC Shim‐pack C8 column (250 × 4.6 mm, 5 µm particle size) using isocratic mobile phase consisting of acetonitrile and 0.02 M dihydrogenphosphate buffer (30:70, v/v) at pH = 5.0. The analysis was performed at a flow rate of 1.0 mL/min with fluorescence detection at 277/313 nm for MET and 298/410 nm for ASP using real‐time programming. The selectivity, linearity of calibration, accuracy, inter‐ and intra‐day precision and recovery were examined as parts of the method validation. The concentration–response relationship was linear over concentration ranges of 0.02‐0.20 and 0.02‐0.40 µg/mL for MET and ASP, respectively, with a limit of detection of 6 and 32 ng/mL for MET and ASP, respectively. The proposed method was successfully applied for the analysis of both MET and ASP in prepared tablets with average recoveries of 99.88 ± 0.65% for MET and 100.44 ± 0.78% for ASP. The results were favourably compared to those obtained by a reference method. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
252.
Allison M Churcher Jose Martin Pujolar Massimo Milan Peter C Hubbard Rute ST Martins Jo?o L Saraiva Mar Huertas Luca Bargelloni Tomaso Patarnello Ilaria AM Marino Lorenzo Zane Adelino VM Canário 《BMC genomics》2014,15(1)
Background
The vertebrate brain plays a critical role in the regulation of sexual maturation and reproduction by integrating environmental information with developmental and endocrine status. The European eel Anguilla anguilla is an important species in which to better understand the neuroendocrine factors that control reproduction because it is an endangered species, has a complex life cycle that includes two extreme long distance migrations with both freshwater and seawater stages and because it occupies a key position within the teleost phylogeny. At present, mature eels have never been caught in the wild and little is known about most aspects of reproduction in A. anguilla. The goal of this study was to identify genes that may be involved in sexual maturation in experimentally matured eels. For this, we used microarrays to compare the gene expression profiles of sexually mature to immature males.Results
Using a false discovery rate of 0.05, a total of 1,497 differentially expressed genes were identified. Of this set, 991 were expressed at higher levels in brains (forebrain and midbrain) of mature males while 506 were expressed at lower levels relative to brains of immature males. The set of up-regulated genes includes genes involved in neuroendocrine processes, cell-cell signaling, neurogenesis and development. Interestingly, while genes involved in immune system function were down-regulated in the brains of mature males, changes in the expression levels of several receptors and channels were observed suggesting that some rewiring is occurring in the brain at sexual maturity.Conclusions
This study shows that the brains of eels undergo major changes at the molecular level at sexual maturity that may include re-organization at the cellular level. Here, we have defined a set of genes that help to understand the molecular mechanisms controlling reproduction in eels. Some of these genes have previously described functions while many others have roles that have yet to be characterized in a reproductive context. Since most of the genes examined here have orthologs in other vertebrates, the results of this study will contribute to the body of knowledge concerning reproduction in vertebrates as well as to an improved understanding of eel biology.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-799) contains supplementary material, which is available to authorized users. 相似文献253.
254.
Nicolli Bellotti de Souza Isabel M de Andrade Paula F Carneiro Guilherme AM Jardim Isadora MM de Melo Eufranio N da Silva Júnior Antoniana Ursine Krettli 《Memórias do Instituto Oswaldo Cruz》2014,109(5):546-552
Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials
as treatment for malarial infection, 19 quinone derivatives with previously reported
structures were also evaluated for blood schizonticide activity against the malaria
parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino
naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol
(13) and phenazines (12-20). Their cytotoxicities were also evaluated against human
hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest
activity against P. falciparum chloroquine-resistant blood-stage parasites (clone
W2), indicated by their low inhibitory concentration for 50% (IC50) of
parasite growth. The therapeutic potential of the active compounds was evaluated
according to the selectivity index, which is a ratio of the cytotoxicity minimum
lethal dose which eliminates 50% of cells and the in vitro IC50.
Naphthoquinones 2 and 5, with activities similar to the reference antimalarial
chloroquine, were also active against malaria in mice and suppressed parasitaemia by
more than 60% in contrast to compound 11 which was inactive. Based on their in vitro
and in vivo activities, compounds 2 and 5 are considered promising molecules for
antimalarial treatment and warrant further study. 相似文献
255.
Wuelton M Monteiro Fernando FA Val André M Siqueira Gabriel P Franca Vanderson S Sampaio Gisely C Melo Anne CG Almeida Marcelo AM Brito Henry M Peixoto Douglas Fuller Quique Bassat Gustavo AS Romero Oliveira Maria Regina F Lacerda Marcus Vinícius G 《Memórias do Instituto Oswaldo Cruz》2014,109(5):553-568
256.
Linda Spiegelberg Sigrid MA Swagemakers Wilfred FJ van IJcken Edwin Oole Eppo B Wolvius Jeroen Essers Joanna AM Braks 《Molecular medicine (Cambridge, Mass.)》2014,20(1):257-269
A side effect of radiation therapy in the head and neck region is injury to surrounding healthy tissues such as irreversible impaired function of the salivary glands. Hyperbaric oxygen therapy (HBOT) is clinically used to treat radiation-induced damage but its mechanism of action is largely unknown. In this study, we investigated the molecular pathways that are affected by HBOT in mouse salivary glands two weeks after radiation therapy by microarray analysis. Interestingly, HBOT led to significant attenuation of the radiation-induced expression of a set of genes and upstream regulators that are involved in processes such as fibrosis and tissue regeneration. Our data suggest that the TGFβ-pathway, which is involved in radiation-induced fibrosis and chronic loss of function after radiation therapy, is affected by HBOT. On the longer term, HBOT reduced the expression of the fibrosis-associated factor α-smooth muscle actin in irradiated salivary glands. This study highlights the potential of HBOT to inhibit the TGFβ-pathway in irradiated salivary glands and to restrain consequential radiation induced tissue injury. 相似文献
257.
Petra Mlcochova Katherine A Sutherland Sarah A Watters Cosetta Bertoli Rob AM de Bruin Jan Rehwinkel Stuart J Neil Gina M Lenzi Baek Kim Asim Khwaja Matthew C Gage Christiana Georgiou Alexandra Chittka Simon Yona Mahdad Noursadeghi Greg J Towers Ravindra K Gupta 《The EMBO journal》2017,36(5):604-616
An unresolved question is how HIV‐1 achieves efficient replication in terminally differentiated macrophages despite the restriction factor SAMHD1. We reveal inducible changes in expression of cell cycle‐associated proteins including MCM2 and cyclins A, E, D1/D3 in macrophages, without evidence for DNA synthesis or mitosis. These changes are induced by activation of the Raf/MEK/ERK kinase cascade, culminating in upregulation of CDK1 with subsequent SAMHD1 T592 phosphorylation and deactivation of its antiviral activity. HIV infection is limited to these G1‐like phase macrophages at the single‐cell level. Depletion of SAMHD1 in macrophages decouples the association between infection and expression of cell cycle‐associated proteins, with terminally differentiated macrophages becoming highly susceptible to HIV‐1. We observe both embryo‐derived and monocyte‐derived tissue‐resident macrophages in a G1‐like phase at frequencies approaching 20%, suggesting how macrophages sustain HIV‐1 replication in vivo. Finally, we reveal a SAMHD1‐dependent antiretroviral activity of histone deacetylase inhibitors acting via p53 activation. These data provide a basis for host‐directed therapeutic approaches aimed at limiting HIV‐1 burden in macrophages that may contribute to curative interventions. 相似文献
258.
259.
Danyel GJ Jennen Addie LJ Vereijken Henk Bovenhuis Richard MPA Crooijmans Jan J van der Poel Martien AM Groenen 《遗传、选种与进化》2005,37(3):215-228
In this report we describe the analysis of an advanced intercross line (AIL) to confirm the quantitative trait locus (QTL) regions found for fatness traits in a previous study. QTL analysis was performed on chromosomes 1, 3, 4, 15, 18, and 27. The AIL was created by random intercrossing in each generation from generation 2 (G2) onwards until generation 9 (G9) was reached. QTL for abdominal fat weight (AFW) and/or percentage abdominal fat (AF%) on chromosomes 1, 3 and 27 were confirmed in the G9 population. In addition, evidence for QTL for body weight at the age of 5 (BW5) and 7 (BW7) weeks and for the percentage of intramuscular fat (IF%) were found on chromosomes 1, 3, 15, and 27. Significant evidence for QTL was detected on chromosome 1 for BW5 and BW7. Suggestive evidence was found on chromosome 1 for AFW, AF% and IF%, on chromosome 15 for BW5, and on chromosome 27 for AF% and IF%. Furthermore, evidence on the chromosome-wise level was found on chromosome 3 for AFW, AF%, and BW7 and on chromosome 27 for BW5. For chromosomes 4 and 18, test statistics did not exceed the significance threshold. 相似文献
260.
John WM Bastiaansen Albart Coster Mario PL Calus Johan AM van Arendonk Henk Bovenhuis 《遗传、选种与进化》2012,44(1):3