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101.
Caccuri AM Antonini G Board PG Flanagan J Parker MW Paolesse R Turella P Federici G Lo Bello M Ricci G 《The Journal of biological chemistry》2001,276(8):5427-5431
Rapid kinetic, spectroscopic, and potentiometric studies have been performed on human Theta class glutathione transferase T2-2 to dissect the mechanism of interaction of this enzyme with its natural substrate GSH. Theta class glutathione transferases are considered to be older than Alpha, Pi, and Mu classes in the evolutionary pathway. As in the more recently evolved GSTs, the activation of GSH in the human Theta enzyme proceeds by a forced deprotonation of the sulfhydryl group (pK(a) = 6.1). The thiol proton is released quantitatively in solution, but above pH 6.5, a protein residue acts as an internal base. Unlike Alpha, Mu, and Pi class isoenzymes, the GSH-binding mechanism occurs via a simple bimolecular reaction with k(on) and k(off) values at least hundred times lower (k(on) = (2.7 +/- 0.8) x 10(4) M(-1) s(-1), k(off) = 36 +/- 9 s(-1), at 37 degrees C). Replacement of Arg-107 by alanine, using site-directed mutagenesis, remarkably increases the pK(a) value of the bound GSH and modifies the substrate binding modality. Y107A mutant enzyme displays a mechanism and rate constants for GSH binding approaching those of Alpha, Mu, and Pi isoenzymes. Comparison of available crystallographic data for all these GSTs reveals an unexpected evolutionary trend in terms of flexibility, which provides a basis for understanding our experimental results. 相似文献
102.
Dedova IV Nikolaeva OP Mikhailova VV dos Remedios CG Levitsky DI 《Biophysical chemistry》2004,110(1-2):119-128
Differential scanning calorimetry was used to examine the effects of cofilin on the thermal unfolding of actin. Stoichiometric binding increases the thermal stability of both G- and F-actin but at sub-saturating concentrations cofilin destabilizes F-actin. At actin:cofilin molar ratios of 1.5-6 the peaks corresponding to stabilized (66-67 degrees C) and destabilized (56-57 degrees C) F-actin are observed simultaneously in the same thermogram. Destabilizing effects of sub-saturating cofilin are highly cooperative and are observed at actin:cofilin molar ratios as low as 100:1. These effects are abolished by the addition of phalloidin or aluminum fluoride. Conversely, at saturating concentrations, cofilin prevents the stabilizing effects of phalloidin and aluminum fluoride on the F-actin thermal unfolding. These results suggest that cofilin stabilizes those actin subunits to which it directly binds, but destabilizes F-actin with a high cooperativity in neighboring cofilin-free regions. 相似文献
103.
Depressed thermogenesis but competent brown adipose tissue recruitment in mice devoid of all hormone-binding thyroid hormone receptors 总被引:1,自引:0,他引:1
Golozoubova V Gullberg H Matthias A Cannon B Vennström B Nedergaard J 《Molecular endocrinology (Baltimore, Md.)》2004,18(2):384-401
We have examined the metabolic role of hormone-binding nuclear thyroid hormone receptors (TRs). Mice devoid of all hormone-binding TRs [TR alpha 1(-/-)beta(-/-) (TR-ablated mice)] had slightly decreased body temperature and much decreased basal metabolic rate, were still able to markedly increase metabolic rate in the cold, but were cold intolerant due to inadequate total heat production at low temperatures. A standard norepinephrine test showed that adrenergically induced thermogenesis could not be activated normally in the TR-ablated mice. This was not due to inadequate recruitment of brown adipose tissue, nor to the absence, decreased recruitment or dysfunction of the uncoupling protein-1. However, isolated brown fat cells were 10-fold desensitized, explaining the lack of response to standard adrenergic stimuli; cell culture experiments demonstrated that this desensitization was not an innate effect. Thus, the cold intolerance was probably not due to inadequate sympathetically induced nonshivering thermogenesis. Additionally, the results indicated that no metabolic effects of thyroid hormones could become manifest in the absence of nuclear TRs, that ligand-bound TRs were needed for euthermia and eumetabolism, but that TRs per se were not required for brown adipose tissue recruitment and uncoupling protein-1 gene expression. 相似文献
104.
The influence of natural surface microtopographies on fouling 总被引:2,自引:0,他引:2
Multiple antifouling strategies of marine organisms may consist of combinations of physical, chemical and mechanical mechanisms. In this study, the role of surface microtopography (< 500 microns) of different marine organisms, such as Cancer pagurus, Mytilus edulis, Ophiura texturata and the eggcase of Scyliorhinus canicula, has been investigated as a possible component of their defence systems. High resolution resin replicates of these natural surface structures were exposed to natural fouling in field experiments. Abundances of recruits were determined and compared to those on untextured, but otherwise identical, control surfaces to quantify the influence of the different microtopographies on fouling rates. Antifouling effects of microtopographies varied with type of microtopography and coloniser species. The surface microtopography of C. pagurus significantly rejected macrofoulers. The surface structures of the eggcase and O. texturata had repellent effects on microfoulers. Barnacle settlement was temporarily reduced on surface microtopographies of M. edulis and the eggcase. These results emphasise the promising nontoxic antifouling properties of microtextured surfaces. 相似文献
105.
Watching the movie scene in which a tarantula crawls on James Bond's chest can make us literally shiver--as if the spider crawled on our own chest. What neural mechanisms are responsible for this "tactile empathy"? The observation of the actions of others activates the premotor cortex normally involved in the execution of the same actions. If a similar mechanism applies to the sight of touch, movies depicting touch should automatically activate the somatosensory cortex of the observer. Here we found using fMRI that the secondary but not the primary somatosensory cortex is activated both when the participants were touched and when they observed someone or something else getting touched by objects. The neural mechanisms enabling our own sensation of touch may therefore be a window also to our understanding of touch. 相似文献
106.
Analysis of the putative regulatory region of the gastric inhibitory polypeptide receptor gene in food-dependent Cushing's syndrome 总被引:1,自引:0,他引:1
Antonini SR N'Diaye N Baldacchino V Hamet P Tremblay J Lacroix A 《The Journal of steroid biochemistry and molecular biology》2004,91(3):171-177
Gastric inhibitory polypeptide (GIP)-dependent Cushing's syndrome (CS) results from the ectopic expression of non-mutated GIP receptor (hGIPR) in the adrenal cortex. We evaluated whether mutations or polymorphisms in the regulatory region of the GIPR gene could lead to this aberrant expression. We studied 9.0kb upstream and 1.3kb downstream of the GIPR gene putative promoter (pProm) by sequencing leukocyte DNA from controls and from adrenal tissues of GIP- and non-GIP-dependent CS patients. The putative proximal promoter region (800 bp) and the first exon and intron of the hGIPR gene were sequenced on adrenal DNA from nine GIP-dependent CS, as well as on leukocyte DNA of nine normal controls. Three variations found in this region were found in all patients and controls; at position -4/-5, an insertion of a T was seen in four out of nine patients and in five out of nine controls. Transient transfection studies conducted in rat GC and mouse Y1 cells showed that the TT allele confers loss of 40% in the promoter activity. The analysis of the 8-kb distal pProm region revealed eight distal single nucleotide polymorphisms (SNPs) without probable association with the disease, since frequencies in patients and controls were very similar. In conclusion, mutations or SNPs in the regulatory region of the GIPR gene are unlikely to underlie GIP-dependent CS. 相似文献
107.
Abian O Grazú V Hermoso J González R García JL Fernández-Lafuente R Guisán JM 《Applied and environmental microbiology》2004,70(2):1249-1251
Three mutations on the penicillin acylase surface (increasing the number of Lys in a defined area) were performed. They did not alter the enzyme's stability and kinetic properties; however, after immobilization on glyoxyl-agarose, the mutant enzyme showed improved stability under all tested conditions (e.g., pH 2.5 at 4 degrees C, pH 5 at 60 degrees C, pH 7 at 55 degrees C, or 60% dimethylformamide), with stabilization factors ranging from 4 to 11 compared with the native enzyme immobilized on glyoxyl-agarose. 相似文献
108.
Brown DR Guantieri V Grasso G Impellizzeri G Pappalardo G Rizzarelli E 《Journal of inorganic biochemistry》2004,98(1):133-143
In this paper, we report the characterization of copper(II) complexes with two prion (PrP) protein peptide fragment analogues (VNITKQHTVTTTT), one with the N-terminus acetylated and the C-terminus amidated (PrP Ac180-193NH2) and the other with both the C- and N-termini free (PrP 180-193). Such peptide sequence almost entirely encompasses the PrPC's helix 2 in the C-terminal region. The stoichiometry, the binding modes and the conformational features of the copper(II) complexes with the above mentioned two peptides were investigated by electrospray ionization-mass spectrometry (ESI-MS), UV-visible (UV-Vis) spectrometry and electron paramagnetic resonance (EPR) spectrometry as well as by circular dichroism (CD) measurements. The binding site location of copper(II) in the structured region of the protein can be here suggested on the basis of our findings that show the involvement of His 187 residue. The similarity of the EPR parameters suggests that the anchoring imidazole residue drives the copper(II) coordination environment towards a common binding motif in different regions of the prion protein. 相似文献
109.
Carru C Zinellu A Galistu F Barca M Pasciu V Lumbau F Sanna B Tadolini B Deiana L 《Journal of biochemical and biophysical methods》2004,61(3):271-281
LDL-oxidation is considered a contributing factor to the development of atherosclerotic lesions. However, to utilise the oxidative state of LDL as a marker of cardiovascular risk, reliable analytical methods for its detection must be defined. We have compared three methods for their capacity to evaluate the difference in the oxidation state of isolated LDL subjected to either dialysis (D-LDL) or gel filtration (F-LDL) to remove EDTA. Their susceptibility to oxidation promoted by Cu(2+) was monitored by following the time course of conjugated diene (CD) and lipid hydroperoxide (ROOH) accumulation. The relative electrophoretic mobility (REM) of the same LDL samples was evaluated by capillary electrophoresis. As measured by all three methods, F-LDL are less prone to oxidation than D-LDL when added with CuSO(4). REM of F-LDL and D-LDL significantly differs already before the addition of the metal catalyst, whereas CD and ROOH contents become significantly different only after it. Besides confirming that a rapid centrifugation followed by gel filtration is a more convenient procedure than dialysis to remove EDTA during LDL isolation, our study suggests the REM of isolated-LDL as the biochemical marker of choice in the evaluation of its oxidative state. 相似文献
110.
The Magellanic Woodpecker (Campephilus magellanicus) is a poorly known species endemic of the Austral Temperate Forests of South America, where it is a potential keystone habitat modifier. Here, I summarize data on the social and breeding biology of this woodpecker, based on 22 active nests located from 1998–2002 in forests from northwestern Argentine Patagonia. Woodpeckers normally traveled in pairs or family parties. In late Austral winter, one to three cavities were selected for completion at each territory. Breeding occurred between mid- to late spring and early to mid-summer, and took about 65 days. Monogamous parents shared duties in nest excavation, incubation and young rearing. Egg length (±SD) measured 34.13±0.79 mm and egg breadth 23.91±0.67 mm, and incubation took roughly 20 days. Nestlings were altricial and remained at the nest for about 45 days. Clutch size was one, occasionally two eggs, and one nestling was produced at all successful nests. Young remained with their family group for up to 2 years or more, and were fed by adults, who normally bred every second year. Nest re-use, nest predation and helpers at the nest were not recorded. Holes were placed (±SD) 8.84±3.71 m high and were 32.3±5.32 cm deep. Entrances (±SD) were 8.92±0.46 cm wide and 15.59±2.54 cm high and mostly oval in shape. Peculiarities of the breeding biology and social behaviour of this species are discussed in the light of patterns common to picids, especially Campephilus spp. 相似文献