全文获取类型
收费全文 | 125篇 |
免费 | 12篇 |
专业分类
137篇 |
出版年
2023年 | 1篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 2篇 |
2017年 | 7篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 5篇 |
2013年 | 12篇 |
2012年 | 6篇 |
2011年 | 7篇 |
2010年 | 6篇 |
2009年 | 6篇 |
2008年 | 6篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 5篇 |
2004年 | 6篇 |
2003年 | 3篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 11篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1960年 | 1篇 |
1958年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有137条查询结果,搜索用时 15 毫秒
1.
2.
The cysteine proteinase 1 (CP1) and cysteine proteinase 2 (CP2) genes of Dictyostelium discoideum encode coordinately expressed mRNA sequences that are inducible by extracellular cAMP. Both genes form part of divergently transcribed gene pairs. The gene proximal to CP1 is coordinately regulated and encodes a protein containing several potential zinc binding domains of the kind found in DNA binding proteins. The gene proximal to CP2 is a constitutively transcribed gene of unknown function. There are multiple, short, G-rich sequence elements between both gene pairs, and deletion of the pair of elements 200 nucleotides upstream from the CP2 gene abolishes cAMP-inducibility. A synthetic oligonucleotide, containing two copies of the G-rich element from the CP1 gene, will reconstitute cAMP-inducibility in the deletion mutant of the CP2 gene. This shows that the elements in the two genes are functionally homologous. Efficient induction requires at least two copies of the CP1 element, but their relative orientation is unimportant. Two copies in an inverted orientation are, however, inactive when moved upstream of their normal position and are incapable of conferring cAMP-inducibility on a heterologous gene. These observations suggest that these sequences are either essential promoter elements, not themselves interacting with the inducer, or that their interaction with a separate class of control sequences is necessary for inducible expression. 相似文献
3.
Hydroxamate-based lysine deacetylase inhibitors (KDACis) are approved for clinical use against certain cancers. However, intrinsic and acquired resistance presents a major problem. Treatment of cells with hydroxamates such as trichostatin A (TSA) leads to rapid preferential acetylation of histone H3 already trimethylated on lysine 4 (H3K4me3), although the importance of this H3K4me3-directed acetylation in the biological consequences of KDACi treatment is not known. We address this utilizing Dictyostelium discoideum strains lacking H3K4me3 due to disruption of the gene encoding the Set1 methyltransferase or mutations in endogenous H3 genes. Loss of H3K4me3 confers resistance to TSA-induced developmental inhibition and delays accumulation of H3K9Ac and H3K14Ac. H3K4me3-directed H3Ac is mediated by Sgf29, a subunit of the SAGA acetyltransferase complex that interacts with H3K4me3 via a tandem tudor domain (TTD). We identify an Sgf29 orthologue in Dictyostelium with a TTD that specifically recognizes the H3K4me3 modification. Disruption of the gene encoding Sgf29 delays accumulation of H3K9Ac and abrogates H3K4me3-directed H3Ac. Either loss or overexpression of Sgf29 confers developmental resistance to TSA. Our results demonstrate that rapid acetylation of H3K4me3 histones regulates developmental sensitivity to TSA. Levels of H3K4me3 or Sgf29 will provide useful biomarkers for sensitivity to this class of chemotherapeutic drug. 相似文献
4.
Proteomic and microarray analyses of the Dictyostelium Zak1-GSK-3 signaling pathway reveal a role in early development 下载免费PDF全文
Strmecki L Bloomfield G Araki T Dalton E Skelton J Schilde C Harwood A Williams JG Ivens A Pears C 《Eukaryotic cell》2007,6(2):245-252
GskA, the Dictyostelium GSK-3 orthologue, is modified and activated by the dual-specificity tyrosine kinase Zak1, and the two kinases form part of a signaling pathway that responds to extracellular cyclic AMP. We identify potential cellular effectors for the two kinases by analyzing the corresponding null mutants. There are proteins and mRNAs that are altered in abundance in only one or the other of the two mutants, indicating that each kinase has some unique functions. However, proteomic and microarray analyses identified a number of proteins and genes, respectively, that are similarly misregulated in both mutant strains. The positive correlation between the array data and the proteomic data is consistent with the Zak1-GskA signaling pathway's functioning by directly or indirectly regulating gene expression. The discoidin 1 genes are positively regulated by the pathway, while the abundance of the H5 protein is negatively regulated. Two of the targets, H5 and discoidin 1, are well-characterized markers for early development, indicating that the Zak1-GskA pathway plays a role in development earlier than previously observed. 相似文献
5.
6.
The experiment was organized in a 3×2 factorial arrangement with three dietary fat blends and a basal (20 mg kg?1 diet) or supplemented (220 mg kg?1) level of α-tocopheryl acetate. Dietary vitamin E and monounsaturated to polyunsaturated fatty acid ratio (dietary MUFA/PUFA) affected muscle α-tocopherol concentration (α-tocopherol [log μg g?1]=0.18 (±0.105)+0.0034 (±0.0003)·dietary α-tocopherol [mg kg?1 diet] (P<0.0001)+0.39 (±0.122)·dietary MUFA/PUFA (P<0.0036)). An interaction between dietary α-tocopherol and dietary MUFA/PUFA exists for microsome α-tocopherol concentration (α-tocopherol [log μg g?1]=1.14 (±0.169) (P<0.0001)+0.0056 (±0.00099)·dietary α-tocopherol [mg kg?1 diet] (P<0.0001)+0.54 (±0.206)·dietary MUFA/PUFA (P<0.0131)?0.0033 (±0.0011)·dietary α-tocopherol [mg kg?1)]×dietary MUFA/PUFA (P<0.0067)), and hexanal concentration in meat (hexanal [ng·g?1]=14807.9 (±1489.8)?28.8 (±10.6) dietary α-tocopherol [mg·kg?1] (P<0.01)?8436.6 (±1701.6)·dietary MUFA/PUFA (P<0.001)+24.0 (±11.22)·dietary α-tocopherol·dietary MUFA/PUFA (P<0.0416)). It is concluded that partial substitution of dietary PUFA with MUFA lead to an increase in the concentration of α-tocopherol in muscle and microsome extracts. An interaction between dietary α-tocopherol and fatty acids exists, in which at low level of dietary vitamin E inclusion, a low MUFA/PUFA ratio leads to a reduction in the concentration of α-tocopherol in microsome extracts and a concentration of hexanal in meat above the expected values. 相似文献
7.
CJ Cooksey 《Biotechnic & histochemistry》2016,91(1):71-76
Rhodamines were first produced in the late 19th century, when they constituted a new class of synthetic dyes. These compounds since have been used to color many things including cosmetics, inks, textiles, and in some countries, food products. Certain rhodamine dyes also have been used to stain biological specimens and currently are widely used as fluorescent probes for mitochondria in living cells. The early history and current biological applications are sketched briefly and an account of the ambiguities, complications and confusions concerning dye identification and nomenclature are discussed. 相似文献
8.
CJ von Ruhland 《Biotechnic & histochemistry》2013,88(7):478-484
Amplification of immunohistochemical markers received considerable attention during the 1980s and 1990s. The amplification approach was largely abandoned following the development of antigen retrieval and reporter amplification techniques, because the latter were incorporated more easily into high throughput automated procedures in industrial and diagnostic laboratories. There remain, however, a number of instances where marker amplification still has much to offer. Consequently, we examined experimentally the utility of an optimized marker amplification technique in diagnostically relevant tissue where either the original signal strength was low or positive sites were visible, but sparsely distributed. Marker amplification in the former case not only improved the visibility of existing positive sites, but also revealed additional sites that previously were undetectable. In the latter case, positive sites were rendered more intense and therefore more easily seen during low magnification examination of large areas of tissue. 相似文献
9.
The results described in the accompanying article support the model in
which glucosylphosphoryldolichol (Glc-P-Dol) is synthesized on the
cytoplasmic face of the ER, and functions as a glucosyl donor for three
Glc-P-Dol:Glc0-2Man9-GlcNAc2-P-P-Dol glucosyltransferases (GlcTases) in the
lumenal compartment. In this study, the enzymatic synthesis and structural
characterization by NMR and electrospray-ionization tandem mass
spectrometry of a series of water-soluble beta-Glc-P-Dol analogs containing
2-4 isoprene units with either the cis - or trans - stereoconfiguration in
the beta-position are described. The water- soluble analogs were (1) used
to examine the stereospecificity of the Glc-P-Dol:Glc0-2Man9GlcNAc2-P-P-Dol
glucosyltransferases (GlcTases) and (2) tested as potential substrates for
a membrane protein(s) mediating the transbilayer movement of Glc-P-Dol in
sealed ER vesicles from rat liver and pig brain. The Glc-P-Dol-mediated
GlcTases in pig brain microsomes utilized [3H]Glc-labeled Glc-P-Dol10,
Glc-P-(omega, c )Dol15, Glc-P(omega, t,t )Dol20, and Glc-P-(omega, t,c
)Dol20as glucosyl donors with [3H]Glc3Man9GlcNAc2-P-P-Dol the major product
labeled in vitro. A preference was exhibited for C15-20 substrates
containing an internal cis -isoprene unit in the beta-position. In
addition, the water-soluble analog, Glc-P-Dol10, was shown to enter the
lumenal compartment of sealed microsomal vesicles from rat liver and pig
brain via a protein-mediated transport system enriched in the ER. The
properties of the ER transport system have been characterized. Glc-
P-Dol10was not transported into or adsorbed by synthetic PC-liposomes or
bovine erythrocytes. The results of these studies indicate that (1) the
internal cis -isoprene units are important for the utilization of Glc-P-Dol
as a glucosyl donor and (2) the transport of the water- soluble analog may
provide an experimental approach to assay the hypothetical "flippase"
proposed to mediate the transbilayer movement of Glc-P-Dol from the
cytoplasmic face of the ER to the lumenal monolayer.
相似文献
10.