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51.
Dagon Y Avraham Y Magen I Gertler A Ben-Hur T Berry EM 《The Journal of biological chemistry》2005,280(51):42142-42148
Although adequate nutrition is essential for optimal neural activity and survival, mild energy restriction may improve cognition and prolong longevity. Energy status is monitored by the cellular AMP-activated protein kinase (AMPK) system, whereas leptin regulates total energy balance. We investigated the roles of AMPK and leptin in cognition and survival under diet restriction (DR). Hippocampal AMPK activity increases with energy restriction. Modest activation (DR to 60%) induces neurogenesis and improves cognition. However, DR to 40% augmented AMPK activity, reduced cognition and catecholamines, and increased neural apoptosis and mortality. Leptin signaling is preserved only in DR to 60%, countering the effects of AMPK "overactivation" by preventing neuroapoptosis, restoring noradrenergic activity and behavioral performance, and increasing longevity. The balance between leptin and AMPK is crucial in determining neuronal fate, cognitive ability, and survival. Should these findings extend to Man, then controlled activation of AMPK may improve neurodegenerative diseases, and leptin may have a new role in treating stress-associated malnutrition. 相似文献
52.
Amira G Ifat M Tal A Hana B Shmuel G Rachel A 《Journal of experimental botany》2005,56(419):2443-2452
With the general aim of elevating the content of the essential amino acid methionine in vegetative tissues of plants, alfalfa (Medicago sativa L.) and tobacco plants, as well as BY2 tobacco suspension cells, were transformed with a beta-zein::3HA gene under the 35S promoter of cauliflower mosaic virus encoding a rumen-stable methionine-rich storage protein of 15 kDa zein. To examine whether soluble methionine content limited the accumulation of the 15 kDa zein::3HA, methionine was first added to the growth medium of the different transgenic plants and the level of the alien protein was determined. Results demonstrated that the added methionine enhanced the accumulation of the 15 kDa zein::3HA in transgenic alfalfa and tobacco BY2 cells, but not in whole transgenic tobacco plants. Next, the endogenous levels of methionine were elevated in the transgenic tobacco and alfalfa plants by crossing them with plants expressing the Arabidopsis cystathionine gamma-synthase (AtCGS) having significantly higher levels of soluble methionine in their leaves. Compared with plants expressing only the 15 kDa zein::3HA, transgenic alfalfa co-expressing both alien genes showed significantly enhanced levels of this protein concurrently with a reduction in the soluble methionine content, thus implying that soluble methionine was incorporated into the 15 kDa zein::3HA. Similar phenomena also occurred in tobacco, but were considerably less pronounced. The results demonstrate that the accumulation of the 15 kDa zein::3HA is regulated in a species-specific manner and that soluble methionine plays a major role in the accumulation of the 15 kDa zein in some plant species but less so in others. 相似文献
53.
RAFTK/Pyk2 activation is mediated by trans-acting autophosphorylation in a Src-independent manner 总被引:1,自引:0,他引:1
The related adhesion focal tyrosine kinase (RAFTK), also known as Pyk2, undergoes autophosphorylation upon its stimulation. This leads to cascades of intracellular signaling that result in the regulation of various cellular activities. However, the molecular mechanism of RAFTK autophosphorylation is not yet known. Using various RAFTK constructs fused with two different tags, we found that the autophosphorylation of RAFTK was mediated by a trans-acting mechanism, not a cis-acting mechanism. In addition, overexpression of kinase-mutated RAFTK inhibited wild type RAFTK autophosphorylation in a dose-dependent manner by a trans-acting interaction. Trans-acting autophosphorylation was also observed between endogenous and exogenous RAFTK upon potassium depolarization of neuroendocrine PC12 cells. Using immunoprecipitation and affinity chromatography, we detected RAFTK self-association that was not affected by deletion of a single region or domain of RAFTK. Furthermore, RAFTK autophosphorylation occurred only at site Tyr402 in a Src kinase activity-independent manner. However, Src significantly enhanced RAFTK-mediated paxillin phosphorylation, suggesting a key role for Src in RAFTK activation and phosphorylation of downstream substrates. Our results indicate that the activation of RAFTK occurs in several steps. First, upon stimulus, RAFTK trans-autophosphorylates Tyr402. Second, phosphorylated Tyr402 recruits and activates Src kinase that in turn phosphorylates RAFTK and enhances its kinase activity. Lastly, the enhanced RAFTK activity induces the activation of downstream signaling molecules. Taken together, these studies provide insights into the molecular mechanism of RAFTK autophosphorylation and the specific role of Src in the regulation of RAFTK activation. 相似文献
54.
Vogg G Fischer S Leide J Emmanuel E Jetter R Levy AA Riederer M 《Journal of experimental botany》2004,55(401):1401-1410
Cuticular waxes play a pivotal role in limiting transpirational water loss across the plant surface. The correlation between the chemical composition of the cuticular waxes and their function as a transpiration barrier is still unclear. In the present study, intact tomato fruits (Lycopersicon esculentum) are used, due to their astomatous surface, as a novel integrative approach to investigate this composition- function relationship: wax amounts and compositions of tomato were manipulated before measuring unbiased cuticular transpiration. First, successive mechanical and extractive wax-removal steps allowed the selective modification of epi- and intracuticular wax layers. The epicuticular film consisted exclusively of very-long-chain aliphatics, while the intracuticular compartment contained large quantities of pentacyclic triterpenoids as well. Second, applying reverse genetic techniques, a loss-of-function mutation with a transposon insertion in a very-long-chain fatty acid elongase beta-ketoacyl-CoA synthase was isolated and characterized. Mutant leaf and fruit waxes were deficient in n-alkanes and aldehydes with chain lengths beyond C30, while shorter chains and branched hydrocarbons were not affected. The mutant fruit wax also showed a significant increase in intracuticular triterpenoids. Removal of the epicuticular wax layer, accounting for one-third of the total wax coverage on wild-type fruits, had only moderate effects on transpiration. By contrast, reduction of the intracuticular aliphatics in the mutant to approximately 50% caused a 4-fold increase in permeability. Hence, the main portion of the transpiration barrier is located in the intracuticular wax layer, largely determined by the aliphatic constituents, but modified by the presence of triterpenoids, whereas epicuticular aliphatics play a minor role. 相似文献
55.
Gal Markel Rona Ortenberg Rachel Seidman Sivan Sapoznik Nira Koren-Morag Michal J. Besser Jair Bar Ronnie Shapira Adva Kubi Gil Nardini Ariel Tessone Avraham J. Treves Eyal Winkler Arie Orenstein Jacob Schachter 《Cancer immunology, immunotherapy : CII》2010,59(2):215-230
It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival. Multivariate analysis with neutralization of LDH showed that increased serum CEACAM1 carries a hazard ratio of 2.40. In vitro, soluble CEACAM1 was derived from CEACAM1(+), but neither from CEACAM1(?) melanoma cells nor from CEACAM1(+) lymphocytes, and directly correlated with the number of CEACAM1(+) melanoma cells. Production of soluble CEACAM1 depended on intact de novo protein synthesis and secretion machineries, but not on metalloproteinase function. An unusually high percentage of CEACAM1(+) circulating NK and T lymphocytes was demonstrated in melanoma patients. CEACAM1 inhibited killing activity in functional assays. CEACAM1 expression could not be induced on lymphocytes by serum from patients with high CEACAM1 expression. Further, expression of other NK receptors was impaired, which collectively indicate on a general abnormality. In conclusion, the systemic dysregulation of CEACAM1 in melanoma patients further denotes the role of CEACAM1 in melanoma and may provide a basis for new tumor monitoring and prognostic platforms. 相似文献
56.
57.
Centrosome amplification has been proposed to contribute to the development of aneuploidy and genome instability. Here, we show that Ataxia-Telangiectasia Mutated (ATM) is localized to the centrosome and co-purified with gamma-tubulin. The importance of ATM in centrosome duplication is demonstrated in Atm-deficient primary mouse embryonic fibroblasts that display centrosome amplification. Interestingly, centrosome amplification was not observed in tumor cell lines derived from Atm and p21 double deficient mouse. Our results also indicate that both p53 and p21 operate in the same pathway as ATM in regulating centrosome biogenesis. Finally, a potential role of ATM in spindle checkpoint regulation is demonstrated by which ATM protein is activated by mitotic stress. These results suggest a role of ATM in spindle checkpoint regulation and indicate that ATM suppresses genome instability and cellular transformation by regulating centrosome biogenesis. 相似文献
58.
Stadthagen G Jackson M Charles P Boudou F Barilone N Huerre M Constant P Liav A Bottova I Nigou J Brando T Puzo G Daffé M Benjamin P Coade S Buxton RS Tascon RE Rae A Robertson BD Lowrie DB Young DB Gicquel B Griffin R 《Microbes and infection / Institut Pasteur》2006,8(8):2245-2253
p-Hydroxybenzoic acid derivatives (p-HBADs) are glycoconjugates secreted by all Mycobacterium tuberculosis isolates whose contribution to pathogenicity remains to be determined. The pathogenicity of three transposon mutants of M. tuberculosis deficient in the biosynthesis of some or all forms of p-HBADs was studied. Whilst the mutants grew similarly to the wild-type strain in macrophages and C57BL/6 mice, two of the mutants induced a more severe and diffuse inflammation in the lungs. The lack of production of some or all forms of p-HBADs in these two mutants also correlated with an increased secretion of the pro-inflammatory cytokines tumour-necrosis factor alpha, interleukin 6 and interleukin 12 in vivo. We propose that the loss of production of p-HBADs by tubercle bacilli results in their diminished ability to suppress the pro-inflammatory response to infection and that this ultimately provokes extensive pulmonary lesions in the C57BL/6 model of tuberculosis infection. 相似文献
59.
Shitzer A 《International journal of biometeorology》2006,50(4):215-223
A first order analytical approximation of steady-state heat conduction in a hollow cylinder exchanging heat at its external
surface by convection with a cold and windy environment is presented. The model depicts the thermal behavior of certain body
elements, e.g., head/face, when exposed to such environments. The results are presented by dimensionless parameters and facilitate
the estimation of wind chill equivalent temperatures (WCETs). The effects of several variables on determining WCETs were studied
using specific examples, leading to the following generalizations: (1) the conditions assumed for "calm" wind speed appear
to be a dominant factor in determining WCET; (2) the effects, on both (skin) surface temperature and on WCET, of a 1°C change
in environmental temperature appear to be more pronounced than those of a 1 m/s change in wind speed; (3) similarly, predicted
WCETs are more sensitive to the geometrical dimensions assumed for the modeled entity than they are to wind speeds; and (4)
tissue thermal conductivity, the angle at which the convective heat transfer coefficient is measured relative to wind direction,
and the factor used to establish "effective" wind speeds in the domain occupied by humans relative to reported values, all
seem to have relatively small effects on the determination of WCET. These conclusions strongly suggest, among other things,
that for any given combination of environmental conditions, wind chill indices may best be presented as ranges rather than
as single values. This seems to apply even when worst-case scenarios are considered. Also emphasized is the need for careful
and realistic selection of all the parameter values used in the determination of WCETs. 相似文献
60.
Shitzer A 《International journal of biometeorology》2006,50(4):224-232
The wind-chill index (WCI), developed in Antarctica in the 1940s and recently updated by the weather services in the USA and
Canada, expresses the enhancement of heat loss in cold climates from exposed body parts, e.g., face, due to wind. The index
provides a simple and practical means for assessing the thermal effects of wind on humans outdoors. It is also used for indicating
weather conditions that may pose adverse risks of freezing at subfreezing environmental temperatures. Values of the WCI depend
on a number of parameters, i.e, temperatures, physical properties of the air, wind speed, etc., and on insolation and evaporation.
This paper focuses on the effects of various empirical correlations used in the literature for calculating the convective
heat transfer coefficients between humans and their environment. Insolation and evaporation are not included in the presentation.
Large differences in calculated values among these correlations are demonstrated and quantified. Steady-state wind-chill-equivalent
temperatures (WCETs) are estimated by a simple, one-dimensional heat-conducting hollow-cylindrical model using these empirical
correlations. Partial comparison of these values with the published “new” WCETs is presented. The variability of the estimated
WCETs, due to different correlations employed to calculate them, is clearly demonstrated. The results of this study clearly
suggest the need for establishing a “gold standard” for estimating convective heat exchange between exposed body elements
and the cold and windy environment. This should be done prior to the introduction and adoption of further modifications to
WCETs and indices. Correlations to estimate the convective heat transfer coefficients between exposed body parts of humans
in windy and cold environments influence the WCETs and need to be standardized. 相似文献