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101.
The PHR (Pam/Highwire/RPM-1) proteins are evolutionarily conserved ubiquitin ligases that regulate axon guidance and synapse formation in Caenorhabditis elegans, Drosophila, zebrafish, and mice. In C. elegans, RPM-1 (Regulator of Presynaptic Morphology-1) functions in synapse formation, axon guidance, axon termination, and postsynaptic GLR-1 trafficking. Acting as an E3 ubiquitin ligase, RPM-1 negatively regulates a MAP kinase pathway that includes: dlk-1, mkk-4, and the p38 MAPK, pmk-3. Here we provide evidence that ppm-1, a serine/threonine phosphatase homologous to human PP2Cα(PPM1A) and PP2Cβ(PPM1B) acts as a second negative regulatory mechanism to control the dlk-1 pathway. We show that ppm-1 functions through its phosphatase activity in a parallel genetic pathway with glo-4 and fsn-1 to regulate both synapse formation in the GABAergic motorneurons and axon termination in the mechanosensory neurons. Our transgenic analysis shows that ppm-1 acts downstream of rpm-1 to negatively regulate the DLK-1 pathway, with PPM-1 most likely acting at the level of pmk-3. Our study provides insight into the negative regulatory mechanisms that control the dlk-1 pathway in neurons and demonstrates a new role for the PP2C/PPM phosphatases as regulators of neuronal development. 相似文献
102.
Spiking neural network simulations incorporating variable transmission delays require synaptic events to be scheduled prior
to delivery. Conventional methods have memory requirements that scale with the total number of synapses in a network. We introduce
novel scheduling algorithms for both discrete and continuous event delivery, where the memory requirement scales instead with
the number of neurons. Superior algorithmic performance is demonstrated using large-scale, benchmarking network simulations. 相似文献
103.
Stafford T Thirkettle M Walton T Vautrelle N Hetherington L Port M Gurney K Redgrave P 《PloS one》2012,7(6):e37749
We present a behavioural task designed for the investigation of how novel instrumental actions are discovered and learnt. The task consists of free movement with a manipulandum, during which the full range of possible movements can be explored by the participant and recorded. A subset of these movements, the 'target', is set to trigger a reinforcing signal. The task is to discover what movements of the manipulandum evoke the reinforcement signal. Targets can be defined in spatial, temporal, or kinematic terms, can be a combination of these aspects, or can represent the concatenation of actions into a larger gesture. The task allows the study of how the specific elements of behaviour which cause the reinforcing signal are identified, refined and stored by the participant. The task provides a paradigm where the exploratory motive drives learning and as such we view it as in the tradition of Thorndike [1]. Most importantly it allows for repeated measures, since when a novel action is acquired the criterion for triggering reinforcement can be changed requiring a new action to be discovered. Here, we present data using both humans and rats as subjects, showing that our task is easily scalable in difficulty, adaptable across species, and produces a rich set of behavioural measures offering new and valuable insight into the action learning process. 相似文献
104.
Sea-Age Variation in Maiden Atlantic Salmon Spawners: Phenotypic Plasticity or Genetic Polymorphism?
Gurney WS Bacon PJ Speirs DC McGinnity P Verspoor E 《Bulletin of mathematical biology》2012,74(3):615-640
Atlantic salmon exhibit a partially heritable polymorphism in which the morphs are distinguished by the duration and location
of the sea-phase of their life-cycle. These morphs co-occur, albeit in characteristically different proportions, in most Scottish
rivers and in both the spring and autumn spawner runs; early running fish being generally associated with upland spawning
locations while late running fish are associated with lowland spawning. Thus, differences in riverine and marine environment
appear to be linked to differences in the relative abundance of the morphs, rather than to the specific morph which is optimally
adapted. In this paper, we report a model-based synthetic study aimed at understanding the key dynamic elements which determine
the long-term stability of this polymorphism, and thus determine the relative abundance of the various sea-age morphs. Given
the recent accumulation of evidence for a genetic basis for the polymorphism, we argue that the key dynamic mechanism which
equalises the realized fitness of the sea-age morphs must be one or more morph-specific density dependencies in the riverine
phase of the life-history. We explore a number of specific mechanisms, firmly based in known salmon biology, by which such
morph-specific density dependence could occur and investigate the robustness of the co-existence which they imply. We conclude
that the co-occurrence of multiple sea-age morphs of Atlantic salmon in Scottish rivers is a stable genetic polymorphism,
maintained by some combination of physical separation and asymmetric competition between spawners of different morphs or the
riverine stages of their offspring or both. 相似文献
105.
M Youle F Rohwer A Stacy M Whiteley BC Steel NJ Delalez AL Nord RM Berry JP Armitage S Kamoun S Hogenhout SP Diggle J Gurney EJ Pollitt A Boetius SC Cary 《Nature reviews. Microbiology》2012,10(8):583-588
Every four years, the Olympic Games plays host to competitors who have built on their natural talent by training for many years to become the best in their chosen discipline. Similar spirit and endeavour can be found throughout the microbial world, in which every day is a competition to survive and thrive. Microorganisms are trained through evolution to become the fittest and the best adapted to a particular environmental niche or lifestyle, and to innovate when the 'rules of the game' are changed by alterations to their natural habitats. In this Essay, we honour the best competitors in the microbial world by inviting them to take part in the inaugural Microbial Olympics. 相似文献
106.
Nian Zhou Wayne Zeller Michael Krohn Herb Anderson Jun Zhang Emmanuel Onua Alex S. Kiselyov Jose Ramirez Guðrún Halldorsdottir Þorkell Andrésson Mark E. Gurney Jasbir Singh 《Bioorganic & medicinal chemistry letters》2009,19(1):123-126
A series of potent and selective EP3 receptor antagonists are described. Utilizing a pharmacophore model developed for the EP3 receptor, a series of 3,4-disubstituted indoles were shown to be high affinity ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors and are potent antagonists in functional assays. 相似文献
107.
108.
Alterations in the structure of new and old forms of simian virus 40 large T antigen (T) defined by age-dependent epitope changes: new T is the same as ATPase-active T. 总被引:3,自引:3,他引:0
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The reactivity of simian virus 40 large T antigen labeled under pulse-chase conditions towards 22 antibodies was measured. Changes in epitope reactivity occurred in several domains of T as it matured, defining major structural alterations that distinguished mature from new molecules. New T reacted best with the same antibodies that bind and inhibit ATPase-active T. These antibodies thus can distinguish new T as a distinct structural and functional form. 相似文献
109.
Georgeta Hategan Alexandre M. Polozov Wayne Zeller Hua Cao Rama K. Mishra Alex S. Kiselyov Jose Ramirez Guðrún Halldorsdottir Þorkell Andrésson Mark E. Gurney Jasbir Singh 《Bioorganic & medicinal chemistry letters》2009,19(23):6797-6800
We have developed a pharmacophore model for the EP3 receptor antagonists based on its endogenous ligand PGE2. This ligand-based design yielded a series of novel peri-substituted [4.3.0] bicyclic aromatics featuring 1-alklyaryl 7-heterocyclic sulfonamide substituents. The synthesized molecules are potent antagonists of human EP3 receptor in vitro and show inhibition of rat platelets aggregation. Optimized derivatives display high selectivity over IP, FP, and other EP receptor panels. 相似文献
110.
Pei-Hsun Cheng Brooke Snyder Dimitri Fillos Chris C Ibegbu Anderson Hsien-Cheng Huang Anthony WS Chan 《BMC cell biology》2008,9(1):20