全文获取类型
收费全文 | 181篇 |
免费 | 21篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 6篇 |
2017年 | 1篇 |
2016年 | 10篇 |
2015年 | 14篇 |
2014年 | 11篇 |
2013年 | 19篇 |
2012年 | 14篇 |
2011年 | 10篇 |
2010年 | 12篇 |
2009年 | 10篇 |
2008年 | 5篇 |
2007年 | 13篇 |
2006年 | 3篇 |
2005年 | 13篇 |
2004年 | 1篇 |
2003年 | 12篇 |
2002年 | 13篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有202条查询结果,搜索用时 15 毫秒
71.
72.
Robin Whelpton Adina T. Michael-Titus Susan M. Stephens Ka Wai Yau David Fengas 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1998,716(1-2)
Gradient elution reversed-phase high-performance liquid chromatographic and capillary electrophoretic separations were optimised to separate substance P (SP) and twelve of its fragments. The methods were applied to a study of the in vivo metabolism of substance P in the rat after intrastriatal injection of the peptide (10 nmol). SP and significant amounts of its N-terminal fragments, SP(1-7) and SP(1-4), were detected but no major C-terminal fragments could be identified. At the concentration studied, the metabolism of SP was shown to follow zero order elimination kinetics with a rate of decay of 0.2 nmol/min. As we have shown that SP(1–4) and SP(1–7) can be produced in vivo in the striatum in relatively large amounts, it is conceivable that these fragments contribute to the overall pharmacological pattern of activity of the parent peptide. 相似文献
73.
The freshwater snail Pseudoplotia scabra Müller (Thiaridae) was first spotted in Lake Kinneret, Israel, in the mid 2000s. In a series of field surveys we followed its spread, documenting how by the end of 2010 this invasive mollusc formed >95 % of the snails in Lake Kinneret, nearly eradicating four native species. 相似文献
74.
Tamar Unger Orly Dym Shira Albeck Yossi Jacobovitch Reut Bernehim David Marom Odelia Pisanty Adina Breiman 《Journal of structural and functional genomics》2010,11(2):113-123
Here we describe the crystal structure of the N-terminal domain of the FK506-binding protein (FKBP) from wheat (wFKBP73),
which is the first structure presenting three FK domains (wFK73_1, wFK73_2 and wFK73_3). The crystal model includes wFK73_2
and wFK73_3 domains and only part of the wFK73_1 domain. The wFK73_1 domain is responsible for binding FK506 and for peptidyl
prolyl cis/trans isomerase (PPIase) activity, while the wFK73_2 and wFK73_3 domains lack these activities. A structure-based
sequence comparison demonstrated that the absence of a large enough hydrophobic pocket important for PPIase activity, and
of the conserved residues necessary for drug binding in the wFK73_2 and wFK73_3 domains explains the lack of these activities
in these domains. Sequence and structural comparison between the three wFKBP73 domains suggest that the wFK73_2 domain is
the most divergent. A structural comparison of the FK domains of wFKBP73 with other FKBPs containing more than one FK domain,
revealed that while the overall architecture of each of the three FK domains displays a typical FKBP fold, their relative
arrangement in space is unique and may have important functional implications. We suggest that the existence of FKBPs with
three FK domains offers additional interactive options for these plant proteins enlarging the overall regulatory functions
of these proteins. 相似文献
75.
Jack-Christophe Cossec Catherine MarquerMai Panchal Adina N. LazarCharles Duyckaerts Marie-Claude Potier 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2010,1801(8):839-845
An increasing number of results implicating cholesterol metabolism in the pathophysiology of Alzheimer's disease (AD) suggest cholesterol as a target for treatment. Research in genetics, pathology, epidemiology, biochemistry, and cell biology, as well as in animal models, suggests that cholesterol, its transporter in the brain, apolipoprotein E, amyloid precursor protein, and amyloid-β all interact in AD pathogenesis. Surprisingly, key questions remain unanswered due to the lack of sensitive and specific methods for assessing cholesterol levels in the brain at subcellular resolution. The aims of this review are not only to discuss the various methods for measuring cholesterol and its metabolites and to catalog results obtained from AD patients but also to discuss some new data linking high plasma membrane cholesterol with modifications of the endocytic compartments. These studies are particularly relevant to AD pathology, since enlarged endosomes are believed to be the first morphological change observed in AD brains, in both sporadic cases and Down syndrome. 相似文献
76.
Introduction
In inflammatory joint disease, such as osteoarthritis (OA), there is an increased level of proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines stimulate the production of matrix metalloproteinases (MMPs), which leads to the degradation of the cartilage extracellular matrix and the loss of key structural components such as sulphated glycosaminoglycan (sGAG) and collagen II. The aim of this study was to examine the therapeutic potential of n-3 polyunsaturated fatty acids (PUFAs) in an in vitro model of cartilage inflammation. 相似文献77.
78.
Ruppert SM Li W Zhang G Carlson AL Limaye A Durum SK Khaled AR 《Biochimica et biophysica acta》2012,1823(10):1877-1893
Bim is a BH3-only member of the Bcl-2 family that enables the death of T-cells. Partial rescue of cytokine-deprived T-cells occurs when Bim and the receptor for the T-cell growth factor, interleukin-7, are deleted, implicating Bim as a possible target of interleukin-7-mediated signaling. Alternative splicing yields three major isoforms: BimEL, BimL and BimS. To study the effect of Bim deficiency and define the function of the major isoforms, Bim-containing and Bim-deficient T-cells, dependent on interleukin-7 for growth, were used. Loss of total Bim in interleukin-7-deprived T-cells resulted in delayed apoptosis. However, loss of Bim also impeded the later degradative phase of autophagy. p62, an autophagy-adaptor protein which is normally degraded, accumulated in Bim deficient cells. To explain this, BimL was found to support acidification of lysosomes that later may associate with autophagic vesicles. Key findings showed that inhibition of lysosomal acidification accelerated death upon interleukin-7 withdrawal only in Bim-containing T-cells. intereukin-7 dependent T-cells lacking Bim were less sensitive to inhibition of lysosomal acidification. BimL co-immunoprecipitated with dynein and Lamp1-containing vesicles, indicating BimL could be an adaptor for dynein to facilitate loading of lysosomes. In Bim deficient T-cells, lysosome-tracking probes revealed vesicles of less acidic pH. Over-expression of BimL restored acidic vesicles in Bim deficient T-cells, while other isoforms, BimEL and BimS, promoted intrinsic cell death. These results reveal a novel role for BimL in lysosomal positioning that may be required for the formation of degradative autolysosomes. 相似文献
79.
Janet I. MacInnes Joanne Mackinnon Adina R. Bujold Kim Ziebell Andrew M. Kropinski John H. E. Nash 《Journal of bacteriology》2012,194(23):6686-6687
Here, we report the first complete genome sequence of Actinobacillus suis, an important opportunistic pathogen of swine. By comparing the genome sequence of A. suis with those of other members of the family Pasteurellaceae, we hope to better understand the role of these organisms in health and disease in swine. 相似文献
80.
Frederico Henning Adina Josepha Renz Shoji Fukamachi Axel Meyer 《Journal of molecular evolution》2010,70(5):405-412
Natural populations of the Midas cichlid species in several different crater lakes in Nicaragua exhibit a conspicuous color
polymorphism. Most individuals are dark and the remaining have a gold coloration. The color morphs mate assortatively and
sympatric population differentiation has been shown based on neutral molecular data. We investigated the color polymorphism
using segregation analysis and a candidate gene approach. The segregation patterns observed in a mapping cross between a gold
and a dark individual were consistent with a single dominant gene as a cause of the gold phenotype. This suggests that a simple
genetic architecture underlies some of the speciation events in the Midas cichlids. We compared the expression levels of several
candidate color genes Mc1r, Ednrb1, Slc45a2, and Tfap1a between the color morphs. Mc1r was found to be up regulated in the gold morph. Given its widespread association in color evolution and role on melanin synthesis,
the Mc1r locus was further investigated using sequences derived from a genomic library. Comparative analysis revealed conserved synteny
in relation to the majority of teleosts and highlighted several previously unidentified conserved non-coding elements (CNEs)
in the upstream and downstream regions in the vicinity of Mc1r. The identification of the CNEs regions allowed the comparison of sequences from gold and dark specimens of natural populations.
No polymorphisms were found between in the population sample and Mc1r showed no linkage to the gold phenotype in the mapping cross, demonstrating that it is not causally related to the color
polymorphism in the Midas cichlid. 相似文献