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beta-Adrenergic receptor (beta AR) blocking agents with intrinsic sympathomimetic activity (ISA) can induce modest increases in beta AR-stimulated activity, such as rate and force of contraction in cardiac tissue. The molecular basis for this activity has been elusive. Previous studies have suggested that these compounds do not stimulate cyclic AMP (cAMP) formation even though activation of adenylate cyclase is the generally accepted mechanism for beta AR promotion of target cell response. In the current studies, we show that several beta AR antagonists with ISA (dichloroisoproterenol, pindolol, and celiprolol) stimulate cAMP accumulation five-, two-, and threefold, respectively, in S49 lymphoma cells, but only if cells are simultaneously incubated with the diterpene forskolin. The KI values observed for inhibition of isoproterenol-stimulated cAMP accumulation or of beta AR [( 125I]iodocyanopindolol) binding for each of the beta blockers with ISA were comparable in magnitude to their respective EC50 values for forskolin-potentiated cAMP accumulation. The forskolin-potentiated responses of these compounds were abolished by the beta AR-antagonist propranolol. These results indicate that the ISA of beta-blocking drugs most likely results from a modest beta AR-mediated stimulation of adenylate cyclase activity. The results further suggest that treatment of target cells with forskolin provides a means to define partial agonism at receptors that are linked to stimulation of adenylate cyclase. 相似文献
74.
Background and aims
Due to the well-known importance of biocrusts for several ecosystem properties linked to soil functionality, we aim to go deeper into the physiological performance of biocrusts components. Possible functional convergences in the physiology of biocrust constituents would facilitate the understanding of both species and genus distributional patterns and improve the possibility of modelling their response to climate change.Methods
We measured gas exchange in the laboratory under controlled conditions of lichen- and moss-dominated biocrusts from four environmentally different locations in Europe. Field data were used to determine the natural hydration sources that drive metabolic activity of biocrusts.Results
Our results show different activity drivers at the four sites. Within site analyses showed similar C fixation for the different crust types in the three sites without hydric stress whilst light use related parameters and respiration at 15 °C were similar in the between sites analyses. There were significant differences in water relations between the biocrusts types, with moss-dominated crusts showing higher maximum and optimum water contents.Conclusions
The functional type approach for biocrusts can be justified from a physiological perspective when similar values are found in the within and between site analyses, the latter indicating habitat independent adaptation patterns. Our multi-site analyses for biocrusts functional performance provide comparisons of C fluxes and water relations in the plant-soil interface that will help to understand the adaptation ability of these communities to possible environmental changes.75.
76.
Optimality models are frequently used in studies of long distance bird migration to help understand and predict migration routes, stopover strategies and fuelling behaviour in a spatially varying environment. These models typically evaluate bird behaviour by focusing on a single optimization currency, such as total migration time or energy-use, without explicitly considering trade-offs between the involved objectives. In this paper, we demonstrate that this classic single-objective approach downplays the importance of variability in bird behaviour. In the light of these considerations, we therefore propose to use a full multi-criteria optimization method to isolate the set of non-dominated, efficient or Pareto optimal solutions. Unlike single-objective optimization where there is only one combination of bird behaviour maximizing fitness, the Pareto solution set represents a range of optimal solutions to conflicting objectives. Our results demonstrate that this multi-objective approach provides important new ways of analyzing how environmental factors and behavioural constraints have driven the evolution of migratory behaviour. 相似文献
77.
Charge transfer reactions that contribute to the photoreactions of the wild type green fluorescent protein (GFP) do not occur in the isolated p-hydroxybenzylidene-imidazolidinone chromophore, demonstrating the role of the protein environment. The high quantum efficiency of the fluorescence photocycle that includes excited state proton transfer and the suppression of non-radiative pathways by the protein environment have been correlated with structural dynamics in the chromophore environment. A low quantum efficiency competing phototransformation reaction of GFP is accompanied by both proton and electron transfer, and closely mimics the charge redistribution that is occurring in the fluorescence photocycle. The protein response to this destabilising event has been demonstrated by cryo-trapping of early products in the reaction pathway and is found to be strong even at 100 K, including displacements of chromophore, protein, solvent and a photogenerated CO2 molecule derived from the decarboxylated Glu 222 side chain. We discuss the ramifications of the observation of strong conformational perturbations below the protein dynamical transition at approximately 200 K, in view of low temperature work on other light sensitive proteins such as myoglobin and bacteriorhodopsin. The proton and electron transfer in the phototransformation pathway mimics the proton and charge transfer which occurs during the fluorescence cycle, which leads to common structural responses in both photoreactions as shown by ultrafast spectroscopy. We review and discuss literature on light-induced and thermal charge transfer events, focusing on recent findings addressing conformational dynamics and implications for thermodynamic properties. 相似文献
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Calum Brown Dave Murray-Rust Jasper van Vliet Shah Jamal Alam Peter H. Verburg Mark D. Rounsevell 《PloS one》2014,9(12)
The globalisation of trade affects land use, food production and environments around the world. In principle, globalisation can maximise productivity and efficiency if competition prompts specialisation on the basis of productive capacity. In reality, however, such specialisation is often constrained by practical or political barriers, including those intended to ensure national or regional food security. These are likely to produce globally sub-optimal distributions of land uses. Both outcomes are subject to the responses of individual land managers to economic and environmental stimuli, and these responses are known to be variable and often (economically) irrational. We investigate the consequences of stylised food security policies and globalisation of agricultural markets on land use patterns under a variety of modelled forms of land manager behaviour, including variation in production levels, tenacity, land use intensity and multi-functionality. We find that a system entirely dedicated to regional food security is inferior to an entirely globalised system in terms of overall production levels, but that several forms of behaviour limit the difference between the two, and that variations in land use intensity and functionality can substantially increase the provision of food and other ecosystem services in both cases. We also find emergent behaviour that results in the abandonment of productive land, the slowing of rates of land use change and the fragmentation or, conversely, concentration of land uses following changes in demand levels. 相似文献
80.
Jasper B. Green Ryan P. J. Lower J. Peter W. Young 《Journal of molecular evolution》2009,69(6):657-667
NfeD-like proteins are widely distributed throughout prokaryotes and are frequently associated with genes encoding stomatin-like
proteins (slipins). Here, we reveal that the NfeD family is ancient and comprises three major groups: NfeD1a, NfeD1b and truncated
NfeD1b. Members of each group are associated with one of four conserved gene partners, three of which have eukaryotic homologues
that are membrane raft associated, namely stomatin, paraslipin (previously SLP-2) and flotillin. The first NfeD group (NfeD1b),
comprises proteins of approximately 460-aa long that have three functional domains: an N-terminal protease, a middle membrane-spanning
region and a soluble C-terminal region rich in β-strands. The nfeD1b gene is adjacent to eoslipin in prokaryotic genomes except in Firmicutes and Deinococci, where yqfA replaces eoslipin. Proteins in the second major group (NfeD1a) are homologous to the C-terminus of NfeD1b which forms a β-barrel-like domain,
and their genes are associated with paraslipin. Using OrthoMCL clustering, we show that nfeD1b genes have become truncated on many independent occasions giving rise to the third major group. These short NfeD homologues
frequently remain associated with their ancestral gene neighbour, resembling NfeD1a in structure, yet are much more related
to full-length NfeD1b; we term these “truncated NfeD1b”. These conserved associations suggest that NfeD proteins are dependent
on gene partners for their function and that the site of interaction may lie within the C-terminal portion that is common
to all NfeD homologues. Although NfeD homologues are confined to prokaryotes, this conserved association could represent an
excellent system to study slipin and flotillin proteins. 相似文献