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31.
Background
PKA, a key regulator of cell signaling, phosphorylates a diverse and important array of target molecules and is spatially docked to members of the A-kinase Anchoring Protein (AKAP) family. AKAR2 is a biosensor which yields a FRET signal in vivo, when phosphorylated by PKA. AKAP5, a prominent member of the AKAP family, docks several signaling molecules including PKA, PDE4D, as well as GPCRs, and is obligate for the propagation of the activation of the mitogen-activated protein kinase cascade from GPCRs to ERK1,2.Results
Using an AKAR2-AKAP5 fusion ??biosensor??, we investigated the spatial-temporal activation of AKAP5 undergoing phosphorylation by PKA in response to ??-adrenergic stimulation. The pattern of PKA activation reported by AKAR2-AKAP5 is a more rapid and spatially distinct from those ??sensed?? by AKAR2-AKAP12. Spatial-temporal restriction of activated PKA by AKAP5 was found to ??shape?? the signaling response. Phosphatase PDE4D tethered to AKAP5 also later reverses within 60?s elevated intracellular cyclic AMP levels stimulated by ??-adrenergic agonist. AKAP12, however, fails to attenuate the rise in cyclic AMP over this time. Fusion of the AKAP5 PDE4D-binding-domain to AKAP12 was found to accelerate a reversal of accumulation of intracellular cyclic AMP.Conclusion
AKAPs, which are scaffolds with tethered enzymes, can ??shape?? the temporal and spatial aspects of cell signaling. 相似文献32.
ABSTRACT: BACKGROUND: PKA, a key regulator of cell signaling, phosphorylates a diverse and important array of target molecules and is spatially docked to members of the A-kinase Anchoring Protein (AKAP) family. AKAR2 is a biosensor which yields a FRET signal in vivo, when phosphorylated by PKA. AKAP5, a prominent member of the AKAP family, docks several signaling molecules including PKA, PDE4D, as well as GPCRs, and is obligate for the propagation of the activation of the mitogen-activated protein kinase cascade from GPCRs to ERK1,2. RESULTS: Using an AKAR2-AKAP5 fusion "biosensor", we investigated the spatial-temporal activation of AKAP5 undergoing phosphorylation by PKA in response to beta-adrenergic stimulation. The pattern of PKA activation reported by AKAR2-AKAP5 is a more rapid and spatially distinct from those "sensed" by AKAR2-AKAP12. Spatial-temporal restriction of activated PKA by AKAP5 was found to "shape" the signaling response. Phosphatase PDE4D tethered to AKAP5 also later reverses within 60 s elevated intracellular cyclic AMP levels stimulated by beta-adrenergic agonist. AKAP12, however, fails to attenuate the rise in cyclic AMP over this time. Fusion of the AKAP5 PDE4D-binding-domain to AKAP12 was found to accelerate a reversal of accumulation of intracellular cyclic AMP. CONCLUSION: AKAPs, which are scaffolds with tethered enzymes, can "shape" the temporal and spatial aspects of cell signaling. 相似文献
33.
Kloss M Decker P Baltz KM Baessler T Jung G Rammensee HG Steinle A Krusch M Salih HR 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(10):6711-6719
Reciprocal interactions between NK cells and dendritic cells have been shown to influence activation of NK cells, maturation, or lysis of dendritic cells and subsequent adaptive immune responses. However, little is known about the crosstalk between monocytes and NK cells and the receptors involved in this interaction. We report in this study that human monocytes, upon TLR triggering, up-regulate MHC class I-Related Chain (MIC) A, but not other ligands for the activating immunoreceptor NKG2D like MICB or UL-16 binding proteins 1-3. MICA expression was associated with CD80, MHC class I and MHC class II up-regulation, secretion of proinflammatory cytokines, and apoptosis inhibition, but was not accompanied by release of MIC molecules in soluble form. TLR-induced MICA on the monocyte cell surface was detected by autologous NK cells as revealed by NKG2D down-regulation. Although MICA expression did not render monocytes susceptible for NK cell cytotoxicity, LPS-treated monocytes stimulated IFN-gamma production of activated NK cells which was substantially dependent on MICA-NKG2D interaction. No enhanced NK cell proliferation or cytotoxicity against third-party target cells was observed after stimulation of NK cells with LPS-activated monocytes. Our data indicate that MICA-NKG2D interaction constitutes a mechanism by which monocytes and NK cells as an early source of IFN-gamma may communicate directly during an innate immune response to infections in humans. 相似文献
34.
35.
Modeling Response of N Addition on C and N Allocation in Scandinavian Norway Spruce Stands 总被引:2,自引:0,他引:2
Because nitrogen is considered to be the major growth-limiting element in boreal forests, the increasing nitrogen availability from deposition should lead to increasing growth. We have tested this assumption by simulating, with a simple model, carbon and nitrogen development in seven long-term fertilization experiments in three Nordic countries. The only differences between sites in the model are climate, the ambient nitrogen deposition, nitrogen fertilization regimes, and the initial conditions at the start of the experiment. The model simulates the observed stand development well as long as nitrogen remains the limiting factor. The simulated retention of deposited nitrogen is in general low (less than 50%), whereas retention of fertilizer nitrogen is higher. This seems to imply that the higher production in the fertilized stands will not be maintained once the fertilization is stopped. The model results also indicate that the major effect of climate on site productivity is through soil processes, not tree physiology. 相似文献
36.
Artificial immune recognition system (AIRS) classification algorithm, which has an important place among classification algorithms in the field of artificial immune systems, has showed an effective and intriguing performance on the problems it was applied. AIRS was previously applied to some medical classification problems including breast cancer, Cleveland heart disease, diabetes and it obtained very satisfactory results. So, AIRS proved to be an efficient artificial intelligence technique in medical field. In this study, the resource allocation mechanism of AIRS was changed with a new one determined by fuzzy-logic. This system, named as fuzzy-AIRS was used as a classifier in the diagnosis of lymph diseases, which is of great importance in medicine. The classifications of lymph diseases dataset taken from University of California at Irvine (UCI) Machine Learning Repository were done using 10-fold cross-validation method. Reached classification accuracies were evaluated by comparing them with reported classifiers in UCI web site in addition to other systems that are applied to the related problems. Also, the obtained classification performances were compared with AIRS with regard to the classification accuracy, number of resources and classification time. While only AIRS algorithm obtained 83.138% classification accuracy, fuzzy-AIRS classified the lymph diseases dataset with 90.00% accuracy. For lymph diseases dataset, fuzzy-AIRS obtained the highest classification accuracy according to the UCI web site. Beside of this success, fuzzy-AIRS gained an important advantage over the AIRS by means of classification time. By reducing classification time as well as obtaining high classification accuracies in the applied datasets, fuzzy-AIRS classifier proved that it could be used as an effective classifier for medical problems. 相似文献
37.
38.
Turnover of Phospholipids in an Unsaturated Fatty Acid Auxotroph of Escherichia coli 总被引:3,自引:1,他引:2 下载免费PDF全文
Peter D. Crowfoot Tetsuo Oka Mojtaba Esfahani Salih J. Wakil 《Journal of bacteriology》1972,112(3):1396-1407
The membrane phospholipids of an unsaturated fatty acid auxotroph of Escherichia coli were found to undergo turnover. These phospholipids were excreted into the culture medium, and were replaced in the cell with newly synthesized phospholipids. Phospholipids of growing cells supplemented with elaidic acid underwent rapid turnover, while those of cells supplemented with oleate, or cis-vaccenate plus palmitoleate, underwent slow turnover. Starvation for required amino acids stimulated this turnover in the latter two cases. Protein was also lost from growing cells. However, after amino acid starvation this loss ceased while phospholipid turnover continued. Electron micrographs of growing cells indicated that large pieces of membrane-like material were separating from the cell surface. 相似文献
39.
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ZKAN OKTAY Salih TUNCAY Tuba KAMAN
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ZCAN Tue SOYLAMI Mesut KARAHAN Muhsin KONUK 《Turkish Journal of Biology》2021,45(4):342
Various recently reported mutant variants, candidate and urgently approved current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many current situations with severe neurological damage and symptoms as well as respiratory tract disorders have begun to be reported. In particular, drug, vaccine, and neutralizing monoclonal antibodies (mAbs) have been developed and are currently being evaluated in clinical trials. Here, we review lessons learned from the use of novel mutant variants of the COVID-19 virus, immunization, new drug solutions, and antibody therapies for infections. Next, we focus on the B 1.1.7, B 1.351, P.1, and B.1.617 lineages or variants of concern that have been reported worldwide, the new manifestations of neurological manifestations, the current therapeutic drug targets for its treatment, vaccine candidates and their efficacy, implantation of convalescent plasma, and neutralization of mAbs. We review specific clinical questions, including many emerging neurological effects and respiratory tract injuries, as well as new potential biomarkers, new studies in addition to known therapeutics, and chronic diseases of vaccines that have received immediate approval. To answer these questions, further understanding of the burden kinetics of COVID-19 and its correlation with neurological clinical outcomes, endogenous antibody responses to vaccines, pharmacokinetics of neutralizing mAbs, and action against emerging viral mutant variants is needed. 相似文献
40.
Heba A. Hagag Salih A. Bazaid El-Sayed S. Abdel-Hameed Mahmood Salman 《Cytotechnology》2014,66(6):913-923
Taif rose (Rosa damascena trigintipetala Dieck) is a sort of damask rose, which is considered as one of the most important economic products of Taif. In this study, the authors investigated the possible cytotoxic, genotoxic, antimutagenic and anticancer effect of concrete and absolute rose oils. The results showed that both concrete and absolute rose oils were cytotoxically and genotoxically safe at a dose of 10 μg/ml when tested on cultures of normal human blood lymphocytes. Also, the results showed significant antimutagenic activity at p < 0.001 for absolute rose oil at the same dose level when tested on cultures of normal human blood lymphocytes supplemented with 300 ng/ml mitomycin C (MMC). On the other hand, concrete and absolute oils exerted a cytotoxic activity against two kinds of human cancer cell lines: HepG2 and MCF7. Concrete oil showed cytotoxic activity against HepG2 and MCF7 with a half maximal inhibitory concentration (IC50) of 16.28 and 18.09 μg/ml, respectively, whereas absolute rose oil showed its cytotoxic activity against HepG2 and MCF7 with an IC50 of 24.94 and 19.69, respectively. From this study, it is concluded that concrete and absolute rose oils are cytotoxically and genotoxically safe at a dose of 10 μg/ml when tested on cultures of normal human blood lymphocytes. In addition, absolute oil has an antimutagenic activity at the same dose. Further investigations are needed to study the activity of higher doses of both oils in vitro and in vivo in experimental animals in order to evaluate the capability of using these oils as therapeutic for treatment of some kinds of cancers. 相似文献