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151.
Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We surmise that there are 3 possibilities to mimic these effects, namely (i) the depletion of cytosolic AcCoA by interfering with its biosynthesis, (ii) the inhibition of acetyltransferases, which are enzymes that transfer acetyl groups from AcCoA to other molecules, mostly leucine residues in cellular proteins, or (iii) the stimulation of deacetylases, which catalyze the removal of acetyl groups from leucine residues. There are several examples of rather nontoxic natural compounds that act as AcCoA depleting agents (e.g., hydroxycitrate), acetyltransferase inhibitors (e.g., anacardic acid, curcumin, epigallocatechin-3-gallate, garcinol, spermidine) or deacetylase activators (e.g., nicotinamide, resveratrol), and that are highly efficient inducers of autophagy in vitro and in vivo, in rodents. Another common characteristic of these agents is their capacity to reduce aging-associated diseases and to confer protective responses against ischemia-induced organ damage. Hence, we classify them as “caloric restriction mimetics” (CRM). Here, we speculate that CRM may mediate their broad health-improving effects by triggering the same molecular pathways that usually are elicited by long-term caloric restriction or short-term starvation and that imply the induction of autophagy as an obligatory event conferring organismal, organ- or cytoprotection. 相似文献
152.
Eric Husson Catherine Humeau Fabrice Blanchard Xavier Framboisier Ivan Marc Isabelle Chevalot 《Journal of Molecular Catalysis .B, Enzymatic》2008,55(3-4):110-117
This paper shows that Lecitase Ultra is an enzyme preparation with a great interest as regioselective biocatalyst in the deprotection of 4 different peracetylated sugars: 1,2,3,4,6-penta-O-acetyl-β-d-galactopyranose (1), 2-acetamido-2-deoxy-1,3,4,6-tetra-O-acetyl-β-d-glucopyranose (4), 1,2,3,4,6-penta-O-acetyl--d-mannopyranose (7) and 2,3,4,6-tetra-O-acetyl-β-d-galacto pyranosyl-(1 → 4)-1,2,3,6-tetra-O-acetyl-β-d-glucopyranoside (9). The enzyme properties (specificity, preference for the per-acetylated sugar and regio-selectivity) were strongly modulated by the immobilization conditions, for example the octyl-LECI preparation was 10 fold more active than the PEI-LECI preparation, while it was more than 40 fold less active against some other substrates. Very interestingly, these changes also affected the regioselectivity, depending on the preparation used it was possible to get free OH groups in anomeric position, position 6 or the mixture of both. Finally, the octyl-LECI preparation did not recognize the -sugars, favouring the β-isomers (in opposition to most commercial lipases or the other LECI preparations). This is potentially useful to obtain pure -peracetylated monosaccharides from a mixture of anomers. 相似文献
153.
Histone acetylation in gene regulation. 总被引:3,自引:0,他引:3
Loredana Verdone Eleonora Agricola Micaela Caserta Ernesto Di Mauro 《Briefings in Functional Genomics and Prot》2006,5(3):209-221
Genetic information is packaged in the highly dynamic nucleoprotein structure called chromatin. Many biological processes are regulated via post-translational modifications of key proteins. Acetylation of lysine residues at the N-terminal histone tails is one of the most studied covalent modifications influencing gene regulation in eukaryotic cells. This review focuses on the role of enzymes involved in controlling both histone and non-histone proteins acetylation levels in the cell, with particular emphasis on their effects on cancer. 相似文献
154.
Reprogramming events of mammalian somatic cells induced by Xenopus laevis egg extracts 总被引:2,自引:0,他引:2
Miyamoto K Furusawa T Ohnuki M Goel S Tokunaga T Minami N Yamada M Ohsumi K Imai H 《Molecular reproduction and development》2007,74(10):1268-1277
It is known that differentiated cells can be reprogrammed to an undifferentiated state in oocyte cytoplasm after nuclear transfer. Recently, some reports suggested that Xenopus egg extracts have the ability to reprogram mammalian somatic cells. Reprogramming events of mammalian cells after Xenopus egg extract treatment and after cell culture of extract-treated cells have not been elucidated. In this experiment, we examined reprogramming events in reversibly permeabilized or nonpermeabilized porcine fibroblast cells after Xenopus egg extract treatment. The Xenopus egg-specific histone B4 was assembled on porcine chromatin and nuclear lamin LIII was incorporated into nuclei. Deacetylation of histone H3 at lysine 9 in extract-treated cells was detected in nonpermeabilized cells, suggesting that a part of reprogramming may be induced even in nonpermeabilized cells. Following culture of extract-treated cells, the cells began to express the pluripotent marker genes such as POU5F1 (OCT4) and SOX2 and to form colonies. Reactivation of the OCT4 gene in extract-treated cells was also confirmed in bovine fibroblasts transformed with an OCT4-EGFP construct. These results suggest that nuclei of mammalian cells can be partially reprogrammed to an embryonic state by Xenopus egg extracts and the remodeled cells partly dedifferentiate after cell culture. A system using egg extracts may be useful for understanding the mechanisms and processes of dedifferentiation and reprogramming of mammalian somatic cells after nuclear transfer. 相似文献
155.
Dibutyltin oxide (DBTO) was first utilized for the deacetylation of steroid and diterpene esters. The results showed the deprotection of acetylated steroids and diterpenes separately with moderate catalysis dibutyltin oxide in methanol selectively removed part acetyl groups of these substrates, whereas several functional groups of the steroids and diterpenes were retained and neither isomerization nor degradation of these substrates was observed. It seems that the acetyl groups with lower steric hindrance or near carbonyl, alkoxy, or hydroxyl groups can be cleaved by the reaction, whereas the acetyl groups with higher steric hindrance or without carbonyl, alkoxy, or hydroxyl groups neighboring were retained under the same conditions. One of the interesting results obtained was the selective hydrolysis of the 3beta-O-acetyl group in the presence of the 6beta group in 3beta,6beta-Di-O-acetyl-5alpha-hydroxypregn-16-en-20-one. This allows for subsequent introduction of one unit at C-3 and the other unit at C-6. This procedure is useful for the synthesis of a series of closely related isomers of 3beta,5alpha,6beta-trihydroxypregn-16-en-20-one and other widespread polyhydroxysteroids in marine organisms and some terrestrial species. 相似文献
156.
157.
研究了甲壳素脱乙酰酶的热稳定性及酶的反应体系作用条件:酶(干重)添加量为40 mg.L-1,甲壳素底物(干重)质量浓度为75 mg.L-1,反应时间为90 m in,金属离子Mg2+对酶活有激活作用,在最适宜反应条件下的酶活为2250 U.L-1。甲壳素脱乙酰酶的酶解方式为外切酶型,酶降解终产物对酶活力有抑制作用,酶对甲壳素有一定的降解作用。 相似文献
158.
Increased metabolite production by deletion of an HDA1‐type histone deacetylase in the phytopathogenic fungi,Magnaporthe oryzae (Pyricularia oryzae) and Fusarium asiaticum 下载免费PDF全文
159.
Lei Chen Yinqiu Zhou Xu Shen Hualiang Jiang Dongxiang Liu 《Journal of inorganic biochemistry》2010,104(2):180-2845
Zn2+ directly participates in catalysis of histone deacetylase (HDAC) Classes I, II, IV enzymes while its role in HDAC Class III activity is not well established. Herein we investigated the effects of Zn2+ on the deacetylase activity of sirtuin 1 (silent mating type information regulation 2 homolog 1, SIRT1). We found that the inherent Zn2+ at the zinc-finger motif of SIRT1 is essential for the structural integrity and the deacetylase activity of SIRT1, whereas the exogenous Zn2+ strongly inhibits the deacetylase activity with an IC50 of 0.82 μM for Zn(Gly)2. SIRT1 activity suppressed by the exogenous Zn2+ can be fully recovered by the metal chelator EDTA but not by the activator resveratrol. We also identified Zn2+ as a noncompetitive inhibitor for the substrates of NAD+ and the acetyl peptide P53-AMC. The 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence titration experiments and site-directed mutagenesis study suggested that the exogenous Zn2+ binds to SIRT1 but not at the zinc-finger motif. These results indicate that Zn2+ plays a dual role in SIRT1 activity. Inherent Zn2+ at the zinc-finger motif is structurally related and essential for SIRT1 activity. On the other hand, Zn2+ may also bind to another site different from the zinc-finger motif or the binding sites for the substrates or resveratrol and act as a potent inhibitor of SIRT1. 相似文献
160.
An improved synthetic approach toward hederacolchiside A1, an antitumor triterpenoid saponin bearing a unique disaccharide moiety, was established. This approach began from a partially protected intermediate and avoided tedious protection-deprotection manipulation. An abnormal ring conformation (1C4) of the center arabinose residue was found in the intermediate, which may account for the unusual regioselectivity between 3-OH and 4-OH of arabinose. Two analogues of hederacolchiside A1 were then facilely prepared by this approach and exhibited significant cytotoxicity in preliminary in vitro assay. 相似文献