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71.
Quantum-dynamical picture of a multistep enzymatic process: reaction catalyzed by phospholipase A(2)
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A quantum-classical molecular dynamics model (QCMD), applying explicit integration of the time-dependent Schr?dinger equation (QD) and Newtonian equations of motion (MD), is presented. The model is capable of describing quantum dynamical processes in complex biomolecular systems. It has been applied in simulations of a multistep catalytic process carried out by phospholipase A(2) in its active site. The process includes quantum-dynamical proton transfer from a water molecule to histidine localized in the active site, followed by a nucleophilic attack of the resulting OH(-) group on a carbonyl carbon atom of a phospholipid substrate, leading to cleavage of an adjacent ester bond. The process has been simulated using a parallel version of the QCMD code. The potential energy function for the active site is computed using an approximate valence bond (AVB) method. The dynamics of the key proton is described either by QD or classical MD. The coupling between the quantum proton and the classical atoms is accomplished via Hellmann-Feynman forces, as well as the time dependence of the potential energy function in the Schr?dinger equation (QCMD/AVB model). Analysis of the simulation results with an Advanced Visualization System revealed a correlated rather than a stepwise picture of the enzymatic process. It is shown that an sp(2)--> sp(3) configurational change at the substrate carbonyl carbon is mostly responsible for triggering the activation process. 相似文献
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73.
Strigolactone biosynthesis in Medicago truncatula and rice requires the symbiotic GRAS-type transcription factors NSP1 and NSP2 总被引:1,自引:0,他引:1
74.
Capsule Predation is a major factor influencing the breeding success of Red-breasted Flycatchers under natural conditions. Aims To examine the breeding success of Red-breasted Flycatchers in relation to nest-site characteristics and time of breeding. Methods Data were collected during seven breeding seasons under natural conditions in Bia?owie?a National Park. We used survival time analysis to estimate changes in survival probability over time and breeding success in relation to first-egg date and nest-site characteristics. Results Offspring fledged successfully from 51% of clutches, but the Kaplan–Meier estimate of survival was lower at 0.43. Of the unsuccessful clutches, 82% were lost to predators. The highest probability of loss was during egg-laying and in the second half of incubation. Breeding success was influenced by the height of the nest above the ground, but no relation to other nest-site characteristics was found. Conclusion To avoid predation Red-breasted Flycatchers build nests in various sites that are more open than most cavity-nesting species. The position of the nest-sites allows the sitting female to observe her surroundings and to escape rapidly from the nest, giving the chance for a replacement clutch. 相似文献
75.
Mammalian skin incorporates a local equivalent of the hypothalamic–pituitary–adrenal (HPA) axis that is critical in coordinating homeostatic responses against external noxious stimuli. Ultraviolet radiation B (UVB) is a skin-specific stressor that can activate this cutaneous HPA axis. Since C57BL/6 (B6) and DBA/2J (D2) strains of mice have different predispositions to sensorineural pathway activation, we quantified expression of HPA axis components at the gene and protein levels in skin incubated ex vivo after UVB or sham irradiation. Urocortin mRNA was up-regulated after all doses of UVB with a maximum level at 50 mJ/cm2 after 12 h for D2 and at 200 mJ/cm2 after 24 h for B6. Proopiomelanocortin mRNA was enhanced after 6 h with the peak after 12 h and at 200 mJ/cm2 for both genotypes of mice. ACTH levels in tissue and media increased after 24 h in B6 but not in D2. UVB stimulated β-endorphin expression was higher in D2 than in B6. Melanocortin receptor 2 mRNA was stimulated by UVB in a dose-dependent manner, with a peak at 200 mJ/cm2 after 12 h for both strains. The expression of Cyp11a1 mRNA — a key mitochondrial P450 enzyme in steroidogenesis, was stimulated at all doses of UVB irradiation, with the most pronounced effect after 12–24 h. UVB radiation caused, independently of genotype, a dose-dependent increase in corticosterone production in the skin, mainly after 24 h of histoculture. Thus, basal and UVB stimulated expression of the cutaneous HPA axis differs as a function of genotype: D2 responds to UVB earlier and with higher amplitude than B6, while B6 shows prolonged (up to 48 h) stress response to a noxious stimulus such as UVB. 相似文献
76.
Emilia J. Sitek Ewa Naro?ańska Beata Pep?ońska S?awomir Filipek Anna Barczak Maria Styczyńska Krzysztof Mlynarczyk Bogna Brockhuis Erik Portelius Dorota Religa Maria Barcikowska Jaros?aw S?awek Cezary ?ekanowski 《PloS one》2013,8(4)
Posterior cortical atrophy is a dementia syndrome with symptoms of cortical visual dysfunction, associated with amyloid plaques and neurofibrillary tangles predominantly affecting visual association cortex. Most patients diagnosed with posterior cortical atrophy will finally develop a typical Alzheimer''s disease. However, there are a variety of neuropathological processes, which could lead towards a clinical presentation of posterior cortical atrophy. Mutations in the presenilin 1 gene, affecting the function of γ-secretase, are the most common genetic cause of familial, early-onset Alzheimer''s disease. Here we present a patient with a clinical diagnosis of posterior cortical atrophy who harbors a novel Presenilin 1 mutation (I211M). In silico analysis predicts that the mutation could influence the interaction between presenilin 1 and presenilin1 enhancer-2 protein, a protein partner within the γ-secretase complex. These findings along with published literature support the inclusion of posterior cortical atrophy on the Alzheimer''s disease spectrum. 相似文献
77.
Jozwicki W Windorbska W Brozyna AA Jochymski C Basta P Sikora J Stasienko E Dutsch-Wicherek M Koper K Wicherek L 《Cell and tissue research》2011,345(3):405-414
RCAS1 is involved in generating the suppressive profile of the tumor microenvironment that helps cancer cells evade immune
surveillance. The status of the cells surrounding the cancer nest may affect both the progression of the cancer and the development
of metastases. In cases of ovarian cancer, a large number of patients do not respond to the applied therapy. The patient’s
response to the applied therapy is directly linked to the status of the tumor microenvironment and the intensity of its suppressive
profile. We analyzed the immunoreactivity of RCAS1 on the cells present in the ovarian cancer microenvironment in patients
with the disease; these cells included macrophages and carcinoma-associated fibroblasts. Later we analyzed the immunoreactivity
levels within these cells, taking into consideration the clinical stage of the cancer and the therapeutic strategy applied,
such as the number of chemotherapy regiments, primary cytoreductive surgery, or the presence of advanced ascites. In the patients
who did not respond to the therapy we observed significantly higher immunoreactivity levels of RCAS1 within the cancer nest
than in those patients who did respond; moreover, in the non-responsive patients we found RCAS1 within both macrophages and
carcinoma-associated fibroblasts. RCAS1 staining may provide information about the intensity of the immuno-suppressive microenvironment
profile found in cases of ovarian cancer and its intensity may directly relate to the clinical outcome of the disease. 相似文献
78.
Stationarity is a crucial yet rarely questioned assumption in the analysis of time series of magneto- (MEG) or electroencephalography (EEG). One key drawback of the commonly used tests for stationarity of encephalographic time series is the fact that conclusions on stationarity are only indirectly inferred either from the Gaussianity (e.g. the Shapiro-Wilk test or Kolmogorov-Smirnov test) or the randomness of the time series and the absence of trend using very simple time-series models (e.g. the sign and trend tests by Bendat and Piersol). We present a novel approach to the analysis of the stationarity of MEG and EEG time series by applying modern statistical methods which were specifically developed in econometrics to verify the hypothesis that a time series is stationary. We report our findings of the application of three different tests of stationarity--the Kwiatkowski-Phillips-Schmidt-Schin (KPSS) test for trend or mean stationarity, the Phillips-Perron (PP) test for the presence of a unit root and the White test for homoscedasticity--on an illustrative set of MEG data. For five stimulation sessions, we found already for short epochs of duration of 250 and 500 ms that, although the majority of the studied epochs of single MEG trials were usually mean-stationary (KPSS test and PP test), they were classified as nonstationary due to their heteroscedasticity (White test). We also observed that the presence of external auditory stimulation did not significantly affect the findings regarding the stationarity of the data. We conclude that the combination of these tests allows a refined analysis of the stationarity of MEG and EEG time series. 相似文献
79.
The first step in the biosynthesis of pterins in bacteria and plants is the conversion of GTP to 7,8-dihydro-d-neopterin triphosphate catalyzed by GTP cyclohydrolase I (GTPCHI). Although GTP has been shown to be a precursor of pterins in archaea, homologues of GTPCHI have not been identified in most archaeal genomes. Here we report the identification of a new GTP cyclohydrolase that converts GTP to 7,8-dihydro-d-neopterin 2',3'-cyclic phosphate, the first intermediate in methanopterin biosynthesis in methanogenic archaea. The enzyme from Methanocaldococcus jannaschii is designated MptA to indicate that it catalyzes the first step in the biosynthesis of methanopterin. MptA is the archetype of a new class of GTP cyclohydrolases that catalyzes a series of reactions most similar to that seen with GTPCHI but unique in that the cyclic phosphate is the product. MptA was found to require Fe2+ for activity. Mutation of conserved histidine residues H200N, H293N, and H295N, expected to be involved in Fe2+ binding, resulted in reduced enzymatic activity but no reduction in the amount of bound iron. 相似文献
80.
Toufic Mayassi Kristin Ladell Herman Gudjonson James E. McLaren Dustin G. Shaw Mai T. Tran Jagoda J. Rokicka Ian Lawrence Jean-Christophe Grenier Vincent van Unen Cezary Ciszewski Matthew Dimaano Hoda E. Sayegh Vinod Kumar Cisca Wijmenga Peter H.R. Green Ranjana Gokhale Hilary Jericho Bana Jabri 《Cell》2019,176(5):967-981.e19