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71.
Copper (Cu) accumulation and tolerance mechanisms in Elsholtzia haichowensis, an indicator plant of Cu mines, were investigated under hydroponics supplied with different concentrations (0.32, 50.0,
100.0 and 200.0 μM) of Cu for 8 days. Cu at 100 and 200 μM significantly decreased the root dry weight, but had no significant
effect on shoot dry weight. The plants grown in the presence of 200 μM Cu accumulated 288 and 7626 μg g−1 DW total Cu in the shoots and roots, respectively. A greater proportion of accumulated Cu was water-soluble accounting for
42–93% of the total Cu content in the shoots. The concentrations of reduced glutathione (GSH) and protein thiols were significantly
enhanced under excess Cu supply. However, the concentrations of these compounds, particularly protein thiols, were much higher
in the leaves than that in the roots. Three UV-absorbing peaks could be eluted out through gel filtration chromatography on
Sephadex G-50. A large amount of Cu was detected in the UV-absorbing peaks in 40–50 and 70–90 ml elution fractions of the
root extract, and in 40–50 and 120–140 ml elution fractions of the leaf extract. The results suggested that the adaptive Cu
tolerance mechanism in E. haichowensis might involve the active participation of protein thiols which had a more important role in the leaves than in the roots. 相似文献
72.
Mass spectrometry (MS) has become a powerful and widely utilized tool in the investigation of protein thiol chemistry, biochemistry, and biology. Very early biochemical studies of metabolic enzymes have brought to light the broad spectrum of reactivity profiles that distinguish cysteine thiols with functions in catalysis and protein stability from other cysteine residues in proteins. The development of MS methods for the analysis of proteins using electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI) coupled with the emergence of high-resolution mass analyzers has been instrumental in advancing studies of thiol modifications, both in single proteins and within the cellular context. This article reviews MS instrumentation and methods of analysis employed in investigations of thiols and their reactivity toward a range of small biomolecules. A selected number of studies are detailed to highlight the advantages brought about by the MS technologies along with the caveats associated with these analyses. 相似文献
73.
Development in the frog, Xenopus laevis, requires the utilization of yolk glyco-lipo-proteins in a temporally- and spatially-dependent manner. The metabolism of the yolk produces hydrogen peroxide (H2O2), a potent reactive oxygen species (ROS). Peroxiredoxins (prdxs) are a family of six anti-oxidant enzymes that, amongst other roles, reduce H2O2. Prdxs reduce H2O2 through a thiol-redox reaction at conserved cysteine residues which results in the creation of disulfide bonds. Recently the thiol-redox reaction of Prdxs has also been implicated in several cell signaling systems. Here we report the cloning and expression patterns during development of six peroxiredoxin homologs from the frog X. laevis. Sequence analysis confirmed their identity as well as their evolutionary relationship with peroxiredoxins from several other species. Using RT-PCR and in situ hybridization analysis we have shown that there is early and robust expression of all six homologs during development. All six X. laevis peroxiredoxins are expressed in neural regions including the brain, eyes, as well as the somites. Different expression patterns for each peroxiredoxin are also observed in the pronephric region, including the proximal and distal tubules. Expression of several peroxiredoxins was also observed in the blood precursors and the olfactory placode. These results suggest important roles for all six peroxiredoxins during early development. These roles may be restricted to their functions as anti-oxidant enzymes, but may also be related to their emerging roles in redox signaling. 相似文献
74.
Dario A. Vitturi Chen-Shan Chen Steven R. Woodcock Sonia R. Salvatore Gustavo Bonacci Jeffrey R. Koenitzer Nicolas A. Stewart Nobunao Wakabayashi Thomas W. Kensler Bruce A. Freeman Francisco J. Schopfer 《The Journal of biological chemistry》2013,288(35):25626-25637
Inflammation, characterized by the activation of both resident and infiltrated immune cells, is accompanied by increased production of oxidizing and nitrating species. Nitrogen dioxide, the proximal nitrating species formed under these conditions, reacts with unsaturated fatty acids to yield nitroalkene derivatives. These electrophilic products modulate protein function via post-translational modification of susceptible nucleophilic amino acids. Nitroalkenes react with Keap1 to instigate Nrf2 signaling, activate heat shock response gene expression, and inhibit NF-κB-mediated signaling, inducing net anti-inflammatory and tissue-protective metabolic responses. We report the purification and characterization of a NADPH-dependent liver enzyme that reduces the nitroalkene moiety of nitro-oleic acid, yielding the inactive product nitro-stearic acid. Prostaglandin reductase-1 (PtGR-1) was identified as a nitroalkene reductase by protein purification and proteomic studies. Kinetic measurements, inhibition studies, immunological and molecular biology approaches as well as clinical analyses confirmed this identification. Overexpression of PtGR-1 in HEK293T cells promoted nitroalkene metabolism to inactive nitroalkanes, an effect that abrogated the Nrf2-dependent induction of heme oxygenase-1 expression by nitro-oleic acid. These results situate PtGR-1 as a critical modulator of both the steady state levels and signaling activities of fatty acid nitroalkenes in vivo. 相似文献
75.
Alejandro E. Leroux Jurgen R. Haanstra Barbara M. Bakker R. Luise Krauth-Siegel 《The Journal of biological chemistry》2013,288(33):23751-23764
In pathogenic trypanosomes, trypanothione synthetase (TryS) catalyzes the synthesis of both glutathionylspermidine (Gsp) and trypanothione (bis(glutathionyl)spermidine (T(SH)2)). Here we present a thorough kinetic analysis of Trypanosoma brucei TryS in a newly developed phosphate buffer system at pH 7.0 and 37 °C, mimicking the physiological environment of the enzyme in the cytosol of bloodstream parasites. Under these conditions, TryS displays Km values for GSH, ATP, spermidine, and Gsp of 34, 18, 687, and 32 μm, respectively, as well as Ki values for GSH and T(SH)2 of 1 mm and 360 μm, respectively. As Gsp hydrolysis has a Km value of 5.6 mm, the in vivo amidase activity is probably negligible. To obtain deeper insight in the molecular mechanism of TryS, we have formulated alternative kinetic models, with elementary reaction steps represented by linear kinetic equations. The model parameters were fitted to the extensive matrix of steady-state data obtained for different substrate/product combinations under the in vivo-like conditions. The best model describes the full kinetic profile and is able to predict time course data that were not used for fitting. This system''s biology approach to enzyme kinetics led us to conclude that (i) TryS follows a ter-reactant mechanism, (ii) the intermediate Gsp dissociates from the enzyme between the two catalytic steps, and (iii) T(SH)2 inhibits the enzyme by remaining bound at its product site and, as does the inhibitory GSH, by binding to the activated enzyme complex. The newly detected concerted substrate and product inhibition suggests that TryS activity is tightly regulated. 相似文献
76.
Background
Glutathione-dependent catalysis is a metabolic adaptation to chemical challenges encountered by all life forms. In the course of evolution, nature optimized numerous mechanisms to use glutathione as the most versatile nucleophile for the conversion of a plethora of sulfur-, oxygen- or carbon-containing electrophilic substances.Scope of review
This comprehensive review summarizes fundamental principles of glutathione catalysis and compares the structures and mechanisms of glutathione-dependent enzymes, including glutathione reductase, glutaredoxins, glutathione peroxidases, peroxiredoxins, glyoxalases 1 and 2, glutathione transferases and MAPEG. Moreover, open mechanistic questions, evolutionary aspects and the physiological relevance of glutathione catalysis are discussed for each enzyme family.Major conclusions
It is surprising how little is known about many glutathione-dependent enzymes, how often reaction geometries and acid–base catalysts are neglected, and how many mechanistic puzzles remain unsolved despite almost a century of research. On the one hand, several enzyme families with non-related protein folds recognize the glutathione moiety of their substrates. On the other hand, the thioredoxin fold is often used for glutathione catalysis. Ancient as well as recent structural changes of this fold did not only significantly alter the reaction mechanism, but also resulted in completely different protein functions.General significance
Glutathione-dependent enzymes are excellent study objects for structure–function relationships and molecular evolution. Notably, in times of systems biology, the outcome of models on glutathione metabolism and redox regulation is more than questionable as long as fundamental enzyme properties are neither studied nor understood. Furthermore, several of the presented mechanisms could have implications for drug development. This article is part of a Special Issue entitled Cellular functions of glutathione. 相似文献77.
78.
Katarzyna A. Broniowska Anne R. Diers Neil Hogg 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
S-Nitrosoglutathione (GSNO) is the S-nitrosated derivative of glutathione and is thought to be a critical mediator of the down stream signaling effects of nitric oxide (NO). GSNO has also been implicated as a contributor to various disease states.Scope of review
This review focuses on the chemical nature of GSNO, its biological activities, the evidence that it is an endogenous mediator of NO action, and implications for therapeutic use.Major conclusions
GSNO clearly exerts its cellular actions through both NO- and S-nitrosation-dependent mechanisms; however, the chemical and biological aspects of this compound should be placed in the context of S-nitrosation as a whole.General significance
GSNO is a central intermediate in formation and degradation of cellular S-nitrosothiols with potential therapeutic applications; thus, it remains an important molecule of study. This article is part of a Special Issue entitled Cellular functions of glutathione. 相似文献79.
Carta S Tassi S Pettinati I Delfino L Dinarello CA Rubartelli A 《The Journal of biological chemistry》2011,286(31):27069-27080
Human myeloid cells activate the NLRP3 inflammasome and secrete interleukin (IL)-1β in response to various Toll-like receptor (TLR) ligands, but the rate of secretion is much higher in primary human monocytes than in cultured macrophages or THP-1 cells. The different myeloid cells also display different redox status under resting conditions and redox response to TLR activation. Resting monocytes display a balanced redox state, with low production of reactive oxygen species (ROS) and antioxidants. TLR engagement induces an effective redox response with increased ROS generation followed by a sustained antioxidant response, parallelled by efficient IL-1β secretion. Drugs blocking ROS production or the antioxidant response prevent the secretion of mature IL-1β but not the biosynthesis of pro-IL-1β, indicating that redox remodeling is responsible for IL-1β processing and release. Unlike monocytes, THP-1 cells and cultured macrophages have up-regulated antioxidant systems that buffer the oxidative hit provided by TLR triggering and suppress the consequent redox response. This aborted redox remodeling is paralleled by low efficiency IL-1β processing and secretion. High doses (5 mM) of H(2)O(2) overcome the high antioxidant capacity of THP-1 cells, restore an efficient redox response, and increase the rate of IL-1β secretion. Together these data indicate that a tightly controlled redox homeostasis in resting cells is a prerequisite for a robust redox response to TLR ligands, in turn necessary for the efficient inflammasome activation. Inflammasome activation by bacterial DNA is not modulated by redox responses, suggesting that redox-dependent regulation of IL-1β secretion is restricted to some inflammasomes including NLRP3 but excluding AIM-2. 相似文献
80.
Described are the syntheses and structures of a phosphonium salt of the anionic ligand O-t-butyl-1,1-dithiooxalate, [PPh3Bz][i-dtotBu] ([PPh3Bz][1]), and of two Cu(I) complexes of this anion, Cu(PPh3)2(η2-i-dtotBu) (2) and Cu(dmp)(PPh3)(η1-i-dtotBu) (3, dmp = 2,9-dimethyl-1,10-phenanthroline). In addition, it was found that the reaction of CuBr2 with i-dtotBu− gives a O-t-butyl-1-perthio-1-thiooxalato complex of copper(I), [BzPh3P][Cu(Br)(S-i-dtotBu)] ([BzPh3P][4]), where [S-i-dtotBu]− is a disulfide-containing anionic ligand. The electronic structure and absorption spectrum of this species were investigated by time dependent DFT methods. 相似文献