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11.
Body condition‐dependent dispersal strategies are common in nature. Although it is obvious that environmental constraints may induce a positive relationship between body condition and dispersal, it is not clear whether positive body conditional dispersal strategies may evolve as a strategy in metapopulations. We have developed an individual‐based simulation model to investigate how body condition–dispersal reaction norms evolve in metapopulations that are characterized by different levels of environmental stochasticity and dispersal mortality. In the model, body condition is related to fecundity and determined either by environmental conditions during juvenile development (adult dispersal) or by those experienced by the mother (natal dispersal). Evolutionarily stable reaction norms strongly depend on metapopulation conditions: positive body condition dependency of dispersal evolved in metapopulation conditions with low levels of dispersal mortality and high levels of environmental stochasticity. Negative body condition‐dependent dispersal evolved in metapopulations with high dispersal mortality and low environmental stochasticity. The latter strategy is responsible for higher dispersal rates under kin competition when dispersal decisions are based on body condition reached at the adult life stage. The evolution of both positive and negative body condition‐dependent dispersal strategies is consequently likely in metapopulations and depends on the prevalent environmental conditions. 相似文献
12.
Raymond W. Bourdeau Enrico Malito Alexandre Chenal Brian L. Bishop Mark W. Musch Mitch L. Villereal Eugene B. Chang Elise M. Mosser Richard F. Rest Wei-Jen Tang 《The Journal of biological chemistry》2009,284(21):14645-14656
Anthrolysin O (ALO) is a pore-forming, cholesterol-dependent cytolysin
(CDC) secreted by Bacillus anthracis, the etiologic agent for
anthrax. Growing evidence suggests the involvement of ALO in anthrax
pathogenesis. Here, we show that the apical application of ALO decreases the
barrier function of human polarized epithelial cells as well as increases
intracellular calcium and the internalization of the tight junction protein
occludin. Using pharmacological agents, we also found that barrier function
disruption requires increased intracellular calcium and protein degradation.
We also report a crystal structure of the soluble state of ALO. Based on our
analytical ultracentrifugation and light scattering studies, ALO exists as a
monomer. Our ALO structure provides the molecular basis as to how ALO is
locked in a monomeric state, in contrast to other CDCs that undergo
antiparallel dimerization or higher order oligomerization in solution. ALO has
four domains and is globally similar to perfringolysin O (PFO) and
intermedilysin (ILY), yet the highly conserved undecapeptide region in domain
4 (D4) adopts a completely different conformation in all three CDCs.
Consistent with the differences within D4 and at the D2-D4 interface, we found
that ALO D4 plays a key role in affecting the barrier function of C2BBE cells,
whereas PFO domain 4 cannot substitute for this role. Novel structural
elements and unique cellular functions of ALO revealed by our studies provide
new insight into the molecular basis for the diverse nature of the CDC
family.Cholesterol-dependent cytolysins
(CDCs)4 are a family
of pore-forming toxins from many organisms, including but not limited to the
genera Archanobacterium, Bacillus, Clostridium, Listeria, and
Streptococcus. Recently, work in vertebrates has revealed that CDCs
and membrane attack complex/perforin superfamily domain-containing proteins
share a similar fold, suggesting that vertebrates use a similar mechanism for
defense against infection (1,
2). A common feature of the CDC
family is the requirement of cholesterol in the membrane to form pores
(3). In addition to
cholesterol, certain members of the family also require a cellular receptor,
such as CD59 for the toxin ILY from Streptococcus intermedius
(4). The specific mechanism by
which CDCs form pores is not completely resolved; however, what is generally
known is that ring-shaped oligomerization at the cellular membrane is followed
by large conformational changes in each unit of the oligomer, resulting in the
insertion of a β-barrel into the cellular membrane
(5). Pore formation results in
a variety of downstream signaling effects, including but not limited to the
influx of Ca2+ into the cell
(6).A good deal is known about structures of the prepore conformation of CDCs.
The crystal structures of prepore PFO, from Clostridium perfringens,
and ILY have previously been elucidated
(7,
8). Each structure shows a
characteristic four-domain architecture, in which domain 4 (D4) is involved in
membrane recognition, domain 3 (D3) is involved in β-sheet insertion, and
domain 2 (D2) is the hinge region that undergoes a large conformational change
(9-11).
Nevertheless, despite the similarities, structural differences in D4
orientation and the conformation of a highly conserved segment named the
undecapeptide region confer functional differences to PFO and ILY
(8). Noting these differences,
we decided to explore the structure and function of another member of the CDC
family, anthrolysin O (ALO).ALO is secreted by Bacillus anthracis, the etiologic agent for
anthrax. ALO is chromosomally encoded by a gene whose regulation is poorly
understood, and it is highly homologous to other members of the CDC family
(12). ALO has been shown to
have hemolytic and cytolytic activity
(13,
14). Although clinical studies
have shown that B. anthracis is weakly hemolytic
(15), anthrax bacteria do
produce biologically relevant amounts of hemolytic ALO, although the levels of
expression are under complex regulation and are dependent on the culture media
and growth conditions (12,
13,
16). At lower concentrations,
ALO can disrupt cell signaling
(13,
14). Search for a cellular
receptor of ALO has lead to the conclusion that it is a TLR4 agonist
(17). However, it is not known
that ALO binds to TLR4 directly and, if so, whether ALO also binds other
cellular receptors.In addition to ALO, B. anthracis secrete ∼400 proteins, termed
the anthrax secretome (18). Of
those, two exotoxins, edema toxin (ET) and lethal toxin (LT) have been
characterized in greatest detail. ET raises intracellular cAMP to pathologic
levels, whereas LT impairs mitogenic and stress responses by inactivating
mitogen-activating protein kinase kinase
(19,
20). The complex interplay
between these two toxins on various aspects of host cellular functions have
been demonstrated
(20-25).
ALO could also work in conjunction with other anthrax virulence factors to
modulate their cellular toxicity. For example, ALO and LF together induce
macrophage apoptosis, whereas ALO and PLC play a redundant role in a murine
inhalation anthrax model (17,
26). Interplay among anthrax
secreted factors on cells relevant to anthrax infection is just beginning to
be understood. This network of interactions is vital to the molecular basis of
how anthrax bacteria interact with the hosts during anthrax infection.Anthrax infection initiates when B. anthracis spores enter the
host through one of three routes: cutaneous, inhalational, or gastrointestinal
(GI) (27,
28). All three routes of
infection can lead to systemic infection and are ultimately lethal. Different
from inhalational anthrax, spores are ingested and germinate on or within the
epithelium of the GI tract in GI anthrax
(29). This is primarily based
on pathological observations that primary lesions of the GI tract are found in
GI anthrax, whereas no primary lesions of the lung are found in inhalational
anthrax (29). Inhalational
anthrax is a disease of choice for biological weapons because of its high
infectivity and mortality
(30). The initiation of GI
anthrax requires much higher doses of spores than inhalational anthrax, and
the molecular basis for the initiation of GI anthrax remains elusive
(31).Since the primary function of GI epithelia is to control the flux of
material into the body, disruption of this barrier can lead to movement of
bacteria into the surrounding tissue
(32). The barrier is produced
by a matrix of transmembrane and membrane-associated proteins. These cell to
cell contacts, or tight junctions, are sometimes altered during bacterial
infection to specifically disrupt the barrier function of epithelial cells.
Using a functional model for the gut epithelium, human gut epithelial Caco-2
brush border expressor (C2BBE) cells, we report that ALO decreases the barrier
function of C2BBE cells through disruption of tight junctions. We also show
that ALO disruption of barrier function is dependent on epithelial cell
polarity. We also present the crystal structure of the soluble state of ALO
and compare it with the known structures of other CDCs. In addition, we show
that ALO exists primarily as a monomer, in contrast to its closely related
homologue PFO, which exists as a dimer. Finally, we used domain swapping to
examine the structural components that confer specificity of ALO to gut
epithelial cells. 相似文献
13.
14.
J Enouf R Bredoux N Bourdeau F Giraud C Le Peuch M Lebret S Levy-Toledano 《Biochimie》1987,69(4):297-304
The effect of cAMP (which involved a 23 kDa protein phosphorylation) has been studied on the Ca2+ uptake and Ca2+ release from a human platelet membrane vesicle fraction. It was tested in the presence of the catalytic subunit of the cAMP-dependent protein kinase (C Sub). The addition of C Sub increased the steady state level of the Ca2+ uptake into the membrane vesicles. The effect was enhanced when tested in the absence of Ca2+ precipitating agent. The response was proportional to the dose of C Sub. Moreover, the effect varied with the Ca2+ concentration. The effect of C Sub has been tested on the inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release. A phosphorylated state of the 23 kDa protein appeared to be necessary. Indeed, a phosphorylation inhibition prevented the IP3 effect and the addition of C Sub increased the percentage of released Ca2+ (without modification of the time course). However, the C Sub dose-dependent response was not linear. The effect of cAMP on the two functions (Ca2+ uptake and Ca2+ release) appears to be different. Therefore, these results led us to suggest a more complex role of cAMP in the regulation of platelet Ca2+ concentration. 相似文献
15.
16.
A central question in evolutionary biology is how coevolutionary history between predator and prey influences their interactions. Contemporary global change and range expansion of exotic organisms impose a great challenge for prey species, which are increasingly exposed to invading non‐native predators, with which they share no evolutionary history. Here, we complete a comprehensive survey of empirical studies of coevolved and naive predator?prey interactions to assess whether a shared evolutionary history with predators influences the magnitude of predator‐induced defenses mounted by prey. Using marine bivalves and gastropods as model prey, we found that coevolved prey and predator‐naive prey showed large discrepancies in magnitude of predator‐induced phenotypic plasticity. Although naive prey, predominantly among bivalve species, did exhibit some level of plasticity – prey exposed to native predators showed significantly larger amounts of phenotypic plasticity. We discuss these results and the implications they may have for native communities and ecosystems. 相似文献
17.
THE ROSETTE DISEASE OF PEANUTS (ARACHIS HYPOGAEA L.) 总被引:1,自引:0,他引:1
18.
Evidence of endoplasmic reticulum-related Ca2+ ATPase in human microvascular endothelial cells 总被引:1,自引:0,他引:1
A Bikfalvi J Enouf R Bredoux A Lompre E Dupuy N Bourdeau S Levy-Toledano G Tobelem 《Experimental cell research》1989,184(1):28-36
We have demonstrated by immunological and molecular methods the presence of a reticulum endoplasmic-related Ca2+-ATPase in human omental microvascular endothelial cells (HOME cells). HOME cells reacted positively with a previously characterized sarcoplasmic reticulum Ca2+-ATPase antibody as demonstrated by indirect immunofluorescence. Western blotting revealed that the antibody recognized a 95-100 kDa protein. 35S-Metabolic labeling led to the detection of a similar protein with which the purified sarcoplasmic reticulum Ca2+-ATPase competed. Dot-blotting experiments indicated that a substantial amount of Ca2+-ATPase was present in HOME cell membranes. In addition, Northern blot analysis using a cDNA probe from cardiac sarcoplasmic reticulum showed the presence of mRNA species of 4-kb. As these experiments were conducted in comparison with cell types with well-defined Ca2+-ATPase in HOME cells. 相似文献
19.
An inhibitor of microRNA-122 reduces viral load in chimpanzees that are chronically infected with hepatitis C virus, suggesting
that such an approach might have therapeutic potential in humans. 相似文献
20.