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161.
Annette Plüddemann J. Claire Hoe Katherine Makepeace E. Richard Moxon Siamon Gordon 《PLoS pathogens》2009,5(2)
Macrophage Scavenger Receptor A (SR-A) is a major non-opsonic receptor for Neisseria meningitidis on mononuclear phagocytes in vitro, and the surface proteins NMB0278, NMB0667, and NMB1220 have been identified as ligands for SR-A. In this study we ascertain the in vivo role of SR-A in the recognition of N. meningitidis MC58 (serogroup B) in a murine model of meningococcal septicaemia. We infected wild-type and SR-A−/− animals intraperitoneally with N. meningitidis MC58 and monitored their health over a period of 50 hours. We also determined the levels of bacteraemia in the blood and spleen, and measured levels of the pro-inflammatory cytokine interleukin-6 (IL-6). The health of SR-A−/− animals deteriorated more rapidly, and they showed a 33% reduction in survival compared to wild-type animals. SR-A−/− animals consistently exhibited higher levels of bacteraemia and increased levels of IL-6, compared to wild-type animals. Subsequently, we constructed a bacterial mutant (MC58-278-1220) lacking two of the SR-A ligands, NMB0278 and NMB1220. Mutation of NMB0667 proved to be lethal. When mice were infected with the mutant bacteria MC58-278-1220, no significant differences could be observed in the health, survival, bacteraemia, and cytokine production between wild-type and SR-A−/− animals. Overall, mutant bacteria appeared to cause less severe symptoms of septicaemia, and a competitive index assay showed that higher levels of wild-type bacteria were recovered when animals were infected with a 1∶1 ratio of wild-type MC58 and mutant MC58-278-1220 bacteria. These data represent the first report of the protective role of SR-A, a macrophage-restricted, non-opsonic receptor, in meningococcal septicaemia in vivo, and the importance of the recognition of bacterial protein ligands, rather than lipopolysaccharide. 相似文献
162.
The impact of bottlenecks on microbial survival,adaptation, and phenotypic switching in host–pathogen interactions 下载免费PDF全文
Richard Moxon Edo Kussell 《Evolution; international journal of organic evolution》2017,71(12):2803-2816
Microbial pathogens and viruses can often maintain sufficient population diversity to evade a wide range of host immune responses. However, when populations experience bottlenecks, as occurs frequently during initiation of new infections, pathogens require specialized mechanisms to regenerate diversity. We address the evolution of such mechanisms, known as stochastic phenotype switches, which are prevalent in pathogenic bacteria. We analyze a model of pathogen diversification in a changing host environment that accounts for selective bottlenecks, wherein different phenotypes have distinct transmission probabilities between hosts. We show that under stringent bottlenecks, such that only one phenotype can initiate new infections, there exists a threshold stochastic switching rate below which all pathogen lineages go extinct, and above which survival is a near certainty. We determine how quickly stochastic switching rates can evolve by computing a fitness landscape for the evolutionary dynamics of switching rates, and analyzing its dependence on both the stringency of bottlenecks and the duration of within‐host growth periods. We show that increasing the stringency of bottlenecks or decreasing the period of growth results in faster adaptation of switching rates. Our model provides strong theoretical evidence that bottlenecks play a critical role in accelerating the evolutionary dynamics of pathogens. 相似文献
163.
CA Lei- CHEN Run-Zheng- YIN Zhi-Jian- ZHANG Guo-Xue- CHEN Wen-Hong- SHUI Yu-Min 《Plant Diversity》2015,37(6):733-736
A new species of Gesneriaceae from Honghe County, Southeastern Yunnan, China, Tremacron hongheense WH. Chen & YM. Shui, is described and illustrated. The new species is similar to Tremacron forrestii Craib, but differs by its leaf blade adaxially sparsely long setose (vs. densely white appressed pubescent and sparsely rusty brown villous), corolla tube outside short white glandular (vs. nearly glabrous), corolla lobes red and thickening at apex, especially adaxial lip (vs. yellow and not thickening), stamens 16-18cm long (vs. 04-12cm long), staminode 05-14cm long (vs. 02-04cm long). 相似文献
164.
Grasslands are one of the most widespread landscapes worldwide, covering approximately one-fifth of the world’s land surface, where grazing is a common practice. How carbon storage responds to grazing in steppes remains poorly understood. We quantified the effects of grazing on community composition and species diversity, and carbon storage in two typical grasslands of northeastern China, one in Horqin and the other one in Hulunbeier. In both grasslands, grazing did not influence plant species diversity. However, it substantially decreased aboveground carbon by 31% and 54% in Horqin and Hulunbeier, respectively. Fenced and grazing treatments showed a similar belowground carbon at both locations. The predominant carbon pool in the study grassland ecosystem was found in the upper 100 cm soil depth, from 98.2 to 99.1% of the total carbon storage. There were no significant effects of grazing on soil carbon neither in the whole profile nor in the uppermost 20 cm soil depth in the two study grasslands. Studies on the effects of varying rangeland management, such as region disparity and grazing systems, may have important consequences on species diversity and carbon partitioning, and thus on rangeland stability and ecosystem functioning. 相似文献
165.
Moxon S Schwach F Dalmay T Maclean D Studholme DJ Moulton V 《Bioinformatics (Oxford, England)》2008,24(19):2252-2253
Recent developments in high-throughput sequencing technologies have generated considerable demand for tools to analyse large datasets of small RNA sequences. Here, we describe a suite of web-based tools for processing plant small RNA datasets. Our tools can be used to identify micro RNAs and their targets, compare expression levels in sRNA loci, and find putative trans-acting siRNA loci. AVAILABILITY: The tools are freely available for use at http://srna-tools.cmp.uea.ac.uk. 相似文献
166.
167.
Craig J Smith Hedley CA Emsley Carole M Gavin Rachel F Georgiou Andy Vail Elisa M Barberan Gregory J del Zoppo John M Hallenbeck Nancy J Rothwell Stephen J Hopkins Pippa J Tyrrell 《BMC neurology》2004,4(1):1-8
Background
Cerebral ischaemia initiates an inflammatory response in the brain and periphery. We assessed the relationship between peak values of plasma interleukin-6 (IL-6) in the first week after ischaemic stroke, with measures of stroke severity and outcome.Methods
Thirty-seven patients with ischaemic stroke were prospectively recruited. Plasma IL-6, and other markers of peripheral inflammation, were measured at pre-determined timepoints in the first week after stroke onset. Primary analyses were the association between peak plasma IL-6 concentration with both modified Rankin score (mRS) at 3 months and computed tomography (CT) brain infarct volume.Results
Peak plasma IL-6 concentration correlated significantly (p < 0.001) with CT brain infarct volume (r = 0.75) and mRS at 3 months (r = 0.72). It correlated similarly with clinical outcome at 12 months or stroke severity. Strong associations were also noted between either peak plasma C-reactive protein (CRP) concentration or white blood cell (WBC) count, and all outcome measures.Conclusions
These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke, and clinical outcome. 相似文献168.
We modeled the neuronal circuits that may underlie a sensory-processing deficit associated with schizophrenia. Schizophrenic
patients have small P50 auditory-evoked responses to click stimuli compared to normal subjects. The P50 auditory-evoked response
is a positive waveform recorded in the EEG approximately 50 ms after the auditory click stimulus. In addition to relatively
small amplitudes, schizophrenic patients do not gate or suppress the P50 auditory-evoked response to the second of two paired-click
stimuli spaced 0.5 s apart. Neuropleptic medication, which decreases dopaminergic neuronal transmission, increases the amplitude
of the P50 auditory-evoked response but does not improve gating. Normal subjects have large P50 auditory-evoked responses
to click stimuli when compared to unmedicated schizophrenic patients, and they gate their response to paired click stimuli
or have smaller P50 auditory-evoked response amplitudes to the second of two click stimuli spaced 0.5 s apart. Schizophrenic
patients do not gate and have similar response amplitudes to both clicks. We hypothesized that the small amplitudes of unmedicated
schizophrenic subjects were due to a state of occlusion whereby excessive background noise in local circuits reduced the ability
of cells to respond synchronously to sensory input, thereby reducing the amplitude of the P50 waveform in the EEG. Because
the P50 auditory-evoked potential amplitudes increased with neuroleptic medication, which reduces dopaminergic neuronal transmission,
we hypothesized a role for dopamine in modulating the signal-to-noise (S/N) in the local circuits responsible for sensory
gating. To test the hypothesis that modulation of the S/N ratio reduces sensory gating, we developed a model of the effects
of dopaminergic neuronal transmission that modulates the S/N in neuronal circuits. The model uses the biologically relevant
computer model of the CA3 region of the hippocampus developed in the companion paper [Moxon et al. (2003) Biol Cybern, this
volume]. Modified Hebb cell assemblies represented the response of the network to the click stimulus. The results of our model
showed that excessive dopaminergic input impaired the ability of cells to respond synchronously to sensory input, which reduced
the amplitudes of the P50 evoked responses.
Received: 3 December 2001 / Accepted: 23 October 2002 / Published online: 28 February 2003
Correspondence to: K.A. Moxon (e-mail: karen.moxon@drexel.edu, Tel.: +1-215-8951959, Fax: +1-215-8954983)
Supported by USPHS, MH01245 & MH58414, MH-01121, and research grants from the Department of Veterans Affairs and the National
Alliance for Research on Schizophrenia and Depression. 相似文献
169.
A model of the CA3 region of the hippocampus was used to simulate the P50 auditory-evoked potential response to repeated
stimuli in order to study the neuronal circuits involved in a sensory-processing deficit associated with schizophrenia. Normal
subjects have a reduced P50 auditory-evoked potential amplitude in response to the second of two paired auditory click stimuli
spaced 0.5 s apart. However, schizophrenic patients do not gate or reduce their response to the second click. They have equal
auditory-evoked response amplitudes to both clicks. When schizophrenic patients were medicated with traditional neuroleptics,
the evoked potential amplitude to both clicks increased, but gating of the second response was not restored or improved. Animal
studies suggest a role for septohippocampal cholinergic activity in sensory gating. We used a computational model of this
system in order to study the relative contributions of local processing and afferent activity in sensory gating. We first
compared the effect of information representation as average firing rate to information representation as cell assemblies
in order to evaluate the best method to represent the response of hippocampal neurons to the auditory click. We then studied
the effects of nicotinic cholinergic input on the response of the network and the effect of GABAB receptor activation on the ability of the local network to suppress the test response. The results of our model showed that
nicotinic cholinergic input from the septum to the hippocampus can control the flow of sensory information from the cortex
into the hippocampus. In addition, postsynaptic GABAB receptor activation was not sufficient to suppress the test response when the interstimulus interval was 500 ms. However,
presynaptic GABAB receptor activity may be responsible for the suppression of the test response at this interstimulus interval.
Received: 3 December 2001 / Accepted: 23 October 2002 / Published online: 28 February 2003
Correspondence to: K. A. Moxon (e-mail: karen.moxon@drexel.edu, Tel.:+1-215-8951959, Fax: +1-215-8954983)
Supported by USPHS, MH01245, MH58414, MH-50787, MH-01121, and research grants from the Department of Veterans Affairs and
the National Alliance for Research on Schizophrenia and Depression. 相似文献
170.