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1.
T lymphocytes recognize antigen in the form of peptides that associate with specific alleles of class I or class II major histocompatibility (MHC) molecules. By contrast with the clear MHC allele-specific binding of peptides to purified class II molecules purified solubilized class I molecules either bind relatively poorly or show degenerate specificity. Using photo-affinity labelling, we demonstrate here the specific interaction of peptides with cell-associated MHC class I molecules and show that this involves metabolically active processes. 相似文献
2.
Advocates of the self-corrective thesis argue that scientific method will refute false theories and find closer approximations to the truth in the long run. I discuss a contemporary interpretation of this thesis in terms of frequentist statistics in the context of the behavioral sciences. First, I identify experimental replications and systematic aggregation of evidence (meta-analysis) as the self-corrective mechanism. Then, I present a computer simulation study of scientific communities that implement this mechanism to argue that frequentist statistics may converge upon a correct estimate or not depending on the social structure of the community that uses it. Based on this study, I argue that methodological explanations of the “replicability crisis” in psychology are limited and propose an alternative explanation in terms of biases. Finally, I conclude suggesting that scientific self-correction should be understood as an interaction effect between inference methods and social structures. 相似文献
3.
Gustavo E. Romero 《Foundations of Science》2016,21(3):455-460
I offer an analysis of the Principle of Sufficient Reason and its relevancy for the scientific endeavour. I submit that the world is not, and cannot be, rational—only some brained beings are. The Principle of Sufficient Reason is not a necessary truth nor a physical law. It is just a guiding metanomological hypothesis justified a posteriori by its success in helping us to unveil the mechanisms that operate in Nature. 相似文献
4.
Jean-Pierre Vilardaga Guillermo Romero Peter A. Friedman Thomas J. Gardella 《Cellular and molecular life sciences : CMLS》2011,68(1):1-13
The parathyroid hormone (PTH) receptor type 1 (PTHR), a G protein-coupled receptor (GPCR), transmits signals to two hormone
systems—PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine—to regulate different biological processes.
PTHR responds to these hormonal stimuli by activating heterotrimeric G proteins, such as GS that stimulates cAMP production. It was thought that the PTHR, as for all other GPCRs, is only active and signals through
G proteins on the cell membrane, and internalizes into a cell to be desensitized and eventually degraded or recycled. Recent
studies with cultured cell and animal models reveal a new pathway that involves sustained cAMP signaling from intracellular
domains. Not only do these studies challenge the paradigm that cAMP production triggered by activated GPCRs originates exclusively
at the cell membrane but they also advance a comprehensive model to account for the functional differences between PTH and
PTHrP acting through the same receptor. 相似文献
5.
I. W. Althaus J. J. Chou A. J. Gonzales R. J. LeMay M. R. Deibel K. -C. Chou F. J. Kezdy D. L. Romero R. C. Thomas P. A. Aristoff W. G. Tarpley F. Reusser 《Cellular and molecular life sciences : CMLS》1994,50(1):23-28
The tetramer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT* and possesses excellent antiviral activity at nontoxic doses in HIV-1 infected lymphocytes grown in tissue culture. Kinetic studies of the HIV-1 RT-catalyzed RNA-directed DNA polymerase activity were carried out in order to determine if the inhibitor interacts with the template: primer or the deoxyribonucleotide triphosphate (dNTP) binding sites of the polymerase. Michaelis-Menten kinetics, which are based on the establishment of a rapid equilibrium between the enzyme and its substrates, proved inadequate for the analysis of the experimental data. The data were thus analyzed using steady-state Briggs-Haldane kinetics assuming that the template:primer binds to the enzyme first, followed by the binding of the dNTP and that the polymerase is a processive enzyme. Based on these assumptions, a velocity equation was derived which allows the calculation of all the specific forward and backward rate constants for the reactions occurring between the enzyme, its substrates and the inhibitor. The calculated rate constants are in agreement with this model and the results indicated that U-9843 acts as a noncompetitive inhibitor with respect to both the template:primer and dNTP binding sites. Hence, U-9843 exhibits the same binding affinity for the free enzyme as for the enzyme-substrate complexes and must inhibit the RT polymerase by interacting with a site distinct from the substrate binding sites. Thus, U-9843 appears to impair an event occurring after the formation of the enzyme-substrate complexes, which involves either an event leading up to the formation of the phosphoester bond, the formation of the ester bond itself or translocation of the enzyme relative to its template:primer following the formation of the ester bond. 相似文献
6.
S. Ohno L. Christian M. Romero R. Dofuku C. Ivey 《Cellular and molecular life sciences : CMLS》1973,29(7):891-891
Zusammenfassung Der amerikanische AalAnguilla rostrata (2n=38; 20M+18A) gehört einer anderen Spezies an als der europäischeAnguilla anguilla (2n=38; 32M+6A).
This work was supported in part by a grant No. CA 05138 from the National Cancer Institute, U.S. Public Health Service. 相似文献
This work was supported in part by a grant No. CA 05138 from the National Cancer Institute, U.S. Public Health Service. 相似文献
7.
Cooperative tandem binding of met repressor of Escherichia coli 总被引:10,自引:0,他引:10
S E Phillips I Manfield I Parsons B E Davidson J B Rafferty W S Somers D Margarita G N Cohen I Saint-Girons P G Stockley 《Nature》1989,341(6244):711-715
We present biochemical and genetic data to support the hypothesis that the Escherichia coli met repressor, MetJ, binds to synthetic and natural operator sequences in tandem arrays such that repression depends not only on the affinity of the DNA-protein interaction, but also on protein-protein contacts along the tandem array. This represents a novel form of regulatory switch. Furthermore, there seems to be homology between the organization of the met and trp operators. 相似文献
8.
This paper dwells upon optimizing the azimuth samp-ling interval of digital surface maps used to model radar ground clutter. The resulting equations can be used... 相似文献
9.
Vanessa Coelho-Santos Renato Socodato Camila Portugal Ricardo A. Leitão Manuel Rito Marcos Barbosa Pierre-Olivier Couraud Ignacio A. Romero Babette Weksler Richard D. Minshall Carlos Fontes-Ribeiro Teresa Summavielle João B. Relvas Ana P. Silva 《Cellular and molecular life sciences : CMLS》2016,73(24):4701-4716
10.
Alexandra Kitz Margarita Dominguez-Villar 《Cellular and molecular life sciences : CMLS》2017,74(22):4059-4075
Since their ‘re-discovery’ more than two decades ago, FOXP3+ regulatory T cells (Tregs) have been an important subject of investigation in the biomedical field and our understanding of the mechanisms that drive their phenotype and function in health and disease has advanced tremendously. During the past few years it has become clear that Tregs are not a terminally differentiated population but show some degree of plasticity, and can, under specific environmental conditions, acquire the phenotype of effector T cells. In particular, recent works have highlighted the acquisition of a Th1-like phenotype by Tregs in several pathological environments. In this review we give an update on the concept of Treg plasticity and the advances in defining the molecular mechanisms that underlie the generation of Th1-like Tregs during an immune response and in different disease settings. 相似文献