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81.
82.
Yvonne Welte James Adjaye Hans R Lehrach Christian RA Regenbrecht 《Cell communication and signaling : CCS》2010,8(1):1-10
Background
The fibroblast growth factor receptor (FGFR) interprets concentration gradients of FGF ligands and structural changes in the heparan sulfate (HS) co-receptor to generate different cellular responses. However, whether the FGFR generates different signals is not known.Results
We have previously shown in rat mammary fibroblasts that in cells deficient in sulfation, and so in HS co-receptor, FGF-2 can only stimulate a transient phosphorylation of p42/44MAPK and so cannot stimulate DNA synthesis. Here we demonstrate that this is because in the absence of HS, FGF-2 fails to stimulate the phosphorylation of the adaptor FGFR substrate 2 (FRS2). In cells possessing the HS co-receptor, FGF-2 elicits a bell-shaped dose response: optimal concentrations stimulate DNA synthesis, but supramaximal concentrations (≥ 100 ng/mL) have little effect. At optimal concentrations (300 pg/mL) FGF-2 stimulates a sustained dual phosphorylation of p42/44MAPK and tyrosine phosphorylation of FRS2. In contrast, 100 ng/mL FGF-2 only stimulates a transient early peak of p42/44MAPK phosphorylation and fails to stimulate appreciably the phosphorylation of FRS2 on tyrosine.Conclusions
These results suggest that the nature of the FGFR signal produced is determined by a combination of the HS co-receptor and the concentration of FGF ligand. Both the phosphorylation of the adaptor FRS2, the kinetics (sustained or transient) of phosphorylation of p42/44(MAPK) are varied, and so differing cellular responses are produced. 相似文献83.
84.
85.
Post-mortem degradation of brain glutamate decarboxylase 总被引:4,自引:0,他引:4
The post-mortem stability of the GABA synthesizing enzyme glutamate decarboxylase (GAD) was studied by using SDS–PAGE and quantitative immunoblotting to measure the rates of degradation of GAD in the cerebral cortex, hippocampus, and cerebellum of rats and mice as a function of time after death. The intact 65- and 67-kDa isoforms of GAD (GAD65 and GAD67) disappeared gradually over a 24-h period. In both rats and mice, the degraded GAD appeared as a band with an apparent molecular mass of 55–57 kDa; no significant amounts of smaller forms were observed. The 55–57 kDa band reacted with antiserum W887, which recognizes a shared epitope at the carboxyl-terminal end of both GADs, indicating that GAD was cleaved near the amino-terminal end of the molecule. GAD67 was cleaved at a site between the amino-terminus and the epitope for antiserum W883 (located within residues 79–93 of GAD67), as antiserum W883 stained a 56-kDa band on the blots. The appearance of degraded GAD paralleled the loss of total GAD (GAD65+GAD67), and after 24 h the 55–57 kDa band accounted for 97, 88, and 59% of the intact GAD lost from rat cerebellum, cerebral cortex and hippocampus. On a percentage basis, GAD67 was degraded more rapidly than was GAD65 in all brain regions studied. The loss of GAD activity was greater in rat than mouse brain, even though the percent loss of intact GAD protein was similar. 相似文献
86.
Stochastic component, inevitable in biological systems, makes problematic the estimation of the model parameters from a single sequence of measurements, despite the complete knowledge of the system. We studied the problem of parameter estimation using individual-based computer simulations of a 'Lotka-Volterra world'. Two kinds (species) of particles--X (preys) and Y (predators)--moved on a sphere according to deterministic rules and at the collision (interaction) of X and Y the particle X was changed to a new particle Y. Birth of preys and death of predators were simulated by addition of X and removal of Y, respectively, according to exponential probability distributions. With this arrangement of the system, the numbers of particles of each kind might be described by the Lotka-Volterra equations. The simulations of the system with low (200-400 particles on average) number of individuals showed unstable oscillations of the population size. In some simulation runs one of the species became extinct. Nevertheless, the oscillations had some generic properties (e.g. mean, in one simulation run, oscillation period, mean ratio of the amplitudes of the consecutive maxima of X and Y numbers, etc.) characteristic for the solutions of the Lotka-Volterra equations. This observation made it possible to estimate the four parameters of the Lotka-Volterra model with high accuracy and good precision. The estimation was performed using the integral form of the Lotka-Volterra equations and two parameter linear regression for each oscillation cycle separately. We conclude that in spite of the irregular time course of the number of individuals in each population due to stochastic intraspecies component, the generic features of the simulated system evolution can provide enough information for quantitative estimation of the system parameters. 相似文献
87.
The phylogenetic origin of the bifunctional tyrosine-pathway protein in the enteric lineage of bacteria 总被引:5,自引:0,他引:5
Because bifunctional enzymes are distinctive and highly conserved products
of relatively infrequent gene-fusion events, they are particularly useful
markers to identify clusters of organisms at different hierarchical levels
of a phylogenetic tree. Within the subdivision of gram-negative bacteria
known as superfamily B, there are two distinctive types of tyrosine-pathway
dehydrogenases: (1) a broad- specificity dehydrogenase (recently termed
cyclohexadienyl dehydrogenase [CDH]) that can utilize either prephenate or
L-arogenate as alternative substrates and (2) a bifunctional CDH that also
posseses chorismate mutase activity. (T-proteins). The bifunctional
T-protein, thought to be encoded by fused ancestral genes for chorismate
mutase and CDH, was found to be present in enteric bacteria (Escherichia,
Shigella, Salmonella, Citrobacter, Klebsiella, Erwinia, Serratia,
Morganella, Cedecea, Kluyvera, Hafnia, Edwardsiella, Yersinia, and Proteus)
and in Aeromonas and Alteromonas. Outside of the latter "enteric lineage,"
the T-protein is absent in other major superfamily-B genera, such as
Pseudomonas (rRNA homology group I), Xanthomonas, Acinetobacter, and
Oceanospirillum. Hence, the T-protein must have evolved after the
divergence of the enteric and Oceanospirillum lineages.
3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase-phe, an early-pathway
isozyme sensitive to feedback inhibition by L- phenylalanine, has been
found in each member of the enteric lineage examined. The absence of both
the T-protein and DAHP synthase-phe elsewhere in superfamily B indicates
the emergence of these character states at approximately the same
evolutionary time.
相似文献
88.
Biotinyl-oligosaccharides are a relatively new generation of saccharide
probes that enable immobilization of desired oligosaccharides on
streptavidin matrices for studies of carbohydrate-protein interactions.
Here we describe the facile preparation of biotinyl-l-3-(2-naphthyl)-
alanine hydrazide (BNAH) derivatives of oligosaccharides, containing a
strong UV absorbing and fluorescent group, in which the ring of the
reducing-end monosaccharide is nonreduced. We evaluate reactivities of
immobilized BNAH- N -glycans with plant lectins that recognize aspects of
the oligosaccharide core or outer-arms. We make some comparisons with
2-amino-6-amidobiotinyl-pyridine (BAP) derivatives obtained by reductive
amination, and 6-(biotinyl)-aminocaproyl-hydrazide (BACH) derivatives which
have a longer spacer-arm. N -Glycan-BNAH and-BAP derivatives have, overall,
comparable reactivities with lectins which recognize N -glycan outer-arms
or the trimannosyl core, but only BNAH and BACH derivatives are bound by
lectins which recognize the non- reduced core. Moreover, with Pisum sativum
agglutinin (PSA) which additionally requires the fucosyl- N-
glycan-asparaginyl core for high affinity binding, the immobilized BNAH
derivative (which is an alanine hydrazide beta-glycoside) can substitute
for the natural beta- glycosylasparaginyl core, whereas the BACH derivative
(aminocaproyl- hydrazide-beta-glycoside) is less effective. BNAH is a
derivatization reagent of choice, therefore, for solid phase
carbohydrate-binding experiments with immobilized N -glycans.
相似文献
89.
Multidimensional heteronuclear NMR studies have been applied to the
resonance assignment and conformational analysis of 13C-enriched
Neu5Acalpha2-3Galbeta1-4Glc. It is demonstrated that three-dimensional
ROESY-HSQC experiments provide through-space distance restraints which
cannot be observed with conventional homonuclear 1H techniques due to
resonance overlap. In particular, connectivities demonstrating the
existence of the "anti" conformation about the Galbeta1-4Glc glycosidic
linkage are unambiguously observed. It is shown that 13C isotopic
enrichment of the trisaccharide at a level >95% enables straightforward
measurement of trans-glycosidic 1H-13C and 13C-13C coupling constants and a
Karplus-type relation is derived for the latter. In total 15 conformational
restraints were obtained for the trisaccharide in aqueous solution, all of
which were in excellent agreement with theoretical parameters computed from
a 5 ns molecular dynamics simulation of the glycan.
相似文献
90.
Molecular phylogenetics of Stenodermatini bat genera: congruence of data from nuclear and mitochondrial DNA 总被引:2,自引:1,他引:1
Van den Bussche RA; Baker RJ; Wichman HA; Hamilton MJ 《Molecular biology and evolution》1993,10(5):944-959
Within the tribe Stenodermatini the systematics of the complex of species
allied with the genus Artibeus has generated several alternative
phylogenetic hypotheses. The most recent treatment recognized four genera
(Artibeus, Dermanura, Enchisthenes, and Koopmania) and suggested that the
most recent common ancestor of these four genera would include the common
ancestor of all other currently recognized Stenodermatini genera except
Sturnira. To test this hypothesis, we examined an EcoRI-defined nuclear
satellite DNA repeat and 402 bp of DNA sequence variation from the
mitochondrial cytochrome b gene. Phylogenetic conclusions based on Southern
blot analyses, in situ hybridization, and mitochondrial DNA sequence data
indicate that Enchisthenes is not closely related to Dermanura, Artibeus,
or Koopmania and that Dermanura, Artibeus, and Koopmania shared a common
ancestor after diverging from the remainder of the Stenodermatini. If our
conclusions are correct, then justification for recognizing Dermanura and
Koopmania as generically distinct from Artibeus must be based on the
magnitude of difference that distinguishes each rather than on the
conclusion that to place them as congeneric with Artibeus creates a
paraphyletic taxon.
相似文献