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101.
Hoshino Y Chiba K Ishino K Fukai T Igarashi Y Yazawa K Mikami Y Ishikawa J 《Journal of bacteriology》2011,193(2):441-448
We identified the biosynthetic gene clusters of the siderophore nocobactin NA. The nbt clusters, which were discovered as genes highly homologous to the mycobactin biosynthesis genes by the genomic sequencing of Nocardia farcinica IFM 10152, consist of 10 genes separately located at two genomic regions. The gene organization of the nbt clusters and the predicted functions of the nbt genes, particularly the cyclization and epimerization domains, were in good agreement with the chemical structure of nocobactin NA. Disruptions of the nbtA and nbtE genes, respectively, reduced and abolished the productivity of nocobactin NA. The heterologous expression of the nbtS gene revealed that this gene encoded a salicylate synthase. These results indicate that the nbt clusters are responsible for the biosynthesis of nocobactin NA. We also found putative IdeR-binding sequences upstream of the nbtA, -G, -H, -S, and -T genes, whose expression was more than 10-fold higher in the low-iron condition than in the high-iron condition. These results suggest that nbt genes are regulated coordinately by IdeR protein in an iron-dependent manner. The ΔnbtE mutant was found to be impaired in cytotoxicity against J774A.1 cells, suggesting that nocobactin NA production is required for virulence of N. farcinica. 相似文献
102.
Local cortical circuit model inferred from power-law distributed neuronal avalanches 总被引:1,自引:0,他引:1
How cortical neurons process information crucially depends on how their local circuits are organized. Spontaneous synchronous
neuronal activity propagating through neocortical slices displays highly diverse, yet repeatable, activity patterns called
“neuronal avalanches”. They obey power-law distributions of the event sizes and lifetimes, presumably reflecting the structure
of local circuits developed in slice cultures. However, the explicit network structure underlying the power-law statistics
remains unclear. Here, we present a neuronal network model of pyramidal and inhibitory neurons that enables stable propagation
of avalanche-like spiking activity. We demonstrate a neuronal wiring rule that governs the formation of mutually overlapping
cell assemblies during the development of this network. The resultant network comprises a mixture of feedforward chains and
recurrent circuits, in which neuronal avalanches are stable if the former structure is predominant. Interestingly, the recurrent
synaptic connections formed by this wiring rule limit the number of cell assemblies embeddable in a neuron pool of given size.
We investigate how the resultant power laws depend on the details of the cell-assembly formation as well as on the inhibitory
feedback. Our model suggests that local cortical circuits may have a more complex topological design than has previously been
thought.
Competing financial interests: The authors declare that they have no competing financial interests.
Action Editor: Peter Latham 相似文献
103.
104.
Kolpakova-Hart E McBratney-Owen B Hou B Fukai N Nicolae C Zhou J Olsen BR 《Developmental biology》2008,321(2):407-419
In vertebrates, coordinated embryonic and postnatal growth of the craniofacial bones and the skull base is essential during the expansion of the rostrum and the brain. Identification of molecules that regulate skull growth is important for understanding the nature of craniofacial defects and for development of non-invasive biologically based diagnostics and therapies.Here we report on spatially restricted growth defects at the skull base and in craniofacial sutures of mice deficient for polycystin-1 (Pkd1). Mutant animals reveal a premature closure of both presphenoid and sphenooccipital synchondroses at the cranial base. Furthermore, knockout mice lacking Pkd1 in neural crest cells are characterized by impaired postnatal growth at the osteogenic fronts in craniofacial sutures that are subjected to tensile forces. Our data suggest that polycystin-1 is required for proliferation of subpopulations of cranial osteochondroprogenitor cells of both mesodermal and neural crest origin during skull growth. However, the Erk1/2 signalling pathway is up-regulated in the Pkd1-deficient skeletal tissue, similarly to that previously reported for polycystic kidney. 相似文献
105.
Owaki T Asakawa M Morishima N Mizoguchi I Fukai F Takeda K Mizuguchi J Yoshimoto T 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(5):2903-2911
IL-27, a member of the IL-6/IL-12 family, activates both STAT1 and STAT3 through its receptor, which consists of WSX-1 and gp130 subunits, resulting in augmentation of Th1 differentiation and suppression of proinflammatory cytokine production. In the present study, we investigated the role of STAT3 in the IL-27-mediated immune functions. IL-27 induced phosphorylation of STAT1, -2, -3 and -5 in wild-type naive CD4+ T cells, but failed to induce that of STAT3 and STAT5 in STAT3-deficient cohorts. IL-27 induced not only proinflammatory responses including up-regulation of ICAM-1, T-box expressed in T cells, and IL-12Rbeta2 and Th1 differentiation, but also anti-inflammatory responses including suppression of proinflammatory cytokine production such as IL-2, IL-4, and IL-13 even in STAT3-deficient naive CD4+ T cells. In contrast, IL-27 augmented c-Myc and Pim-1 expression and induced cell proliferation in wild-type naive CD4+ T cells but not in STAT3-deficient cohorts. Moreover, IL-27 failed to activate STAT3, augment c-Myc and Pim-1 expression, and induce cell proliferation in pro-B BaF/3 transfectants expressing mutant gp130, in which the putative STAT3-binding four Tyr residues in the YXXQ motif of the cytoplasmic region was replaced by Phe. These results suggest that STAT3 is activated through gp130 by IL-27 and is indispensable to IL-27-mediated cell proliferation but not to IL-27-induced Th1 differentiation and suppression of proinflammatory cytokine production. Thus, IL-27 may be a cytokine, which activates both STAT1 and STAT3 through distinct receptor subunits, WSX-1 and gp130, respectively, to mediate its individual immune functions. 相似文献
106.
Kawato M Shirakawa R Kondo H Higashi T Ikeda T Okawa K Fukai S Nureki O Kita T Horiuchi H 《The Journal of biological chemistry》2008,283(1):166-174
Non-hydrolyzable GTP analogues, such as guanosine 5'-(beta, gamma-imido)triphosphate (GppNHp), induce granule secretion from permeabilized platelets in the absence of increased intracellular Ca(2+). Here, we show that the GppNHp-induced dense granule secretion from permeabilized platelets occurred concomitantly with the activation of small GTPase Ral. This secretion was inhibited by the addition of GTP-Ral-binding domain (RBD) of Sec5, which is a component of the exocyst complex known to function as a tethering factor at the plasma membrane for vesicles. We generated an antibody against Sec5-RBD, which abolished the interaction between GTP-Ral and the exocyst complex in vitro. The addition of this antibody inhibited the GppNHp-induced secretion. These data indicate that Ral mediates the GppNHp-induced dense granule secretion from permeabilized platelets through interaction with its effector, the exocyst complex. Furthermore, GppNHp enhanced the Ca(2+) sensitivity of dense granule secretion from permeabilized platelets, and this enhancement was inhibited by Sec5-RBD. In intact platelets, the association between Ral and the exocyst complex was induced by thrombin stimulation with a time course similar to that of dense granule secretion and Ral activation. Taken together, our results suggest that the Ral-exocyst pathway participates in the regulation of platelet dense granule secretion by enhancing the Ca(2+) sensitivity of the secretion. 相似文献
107.
108.
109.
Mutants of Corynebacterium glutamicum that were unable to grow under mild alkaline pH conditions were isolated by mutagenesis. Strain AL-43 exhibiting the highest
sensitivity to alkaline pH among the mutants was selected and used to clone a DNA fragment that could complement the phenotype.
Sequencing and subcloning of the cloned 4.0-kb EcoRI DNA fragment showed that the Cgl1281 gene was responsible for the complementation. The deduced amino acid sequence of Cgl1281
was found to show significant sequence similarity with CzcD, a Me2+/H+(K+) antiporter, from Bacillus subtilis and also possess the features of the cation diffusion facilitator (CDF) family: the presence of 6 putative transmembrane
segments and a signature sequence, indicating that the gene product is a member of the CDF family. Chromosomal disruption
of the Cgl1281 rendered C. glutamicum cells sensitive to alkaline pH as well as cobalt, while expression of the gene from a plasmid restored alkali-tolerance to
the wild-type level and also led to increased cobalt resistance. These results demonstrated that the putative transporter
of the CDF family mediates resistance to cobalt and also plays a physiological role in alkaline pH tolerance in C. glutamicum. 相似文献
110.