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51.
52.
D. R. Knott 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2001,103(1):171-177
The action of the gene Sr6 for stem rust resistance in wheat is affected by temperature, light, and the particular susceptible parent with which a line
carrying Sr6 has been crossed. Two experiments were carried out to determine whether the effect of the susceptible parents was due to
modifier genes, the general genetic background, or interallelic interactions. The data indicated that the susceptible parents
carried different sr6 alleles that interacted with Sr6, possibly in a paramutation-like process. In the course of the study, a number of anomalous results were obtained that may
be due to the action of transposable elements.
Received: 18 February 2000 / Accepted: 31 October 2000 相似文献
53.
Seagrass habitats worldwide are degrading and becoming fragmented, threatening the important ecosystem services they provide. Fauna associated with seagrasses, particularly cryptic species, are expected to respond to these changes, but are difficult to detect at ecologically meaningful scales using non-extractive techniques. We used a small, wide-angle camera (GoPro) and a small quantity of bait positioned within the canopy of Posidonia australis meadows in Jervis Bay, New South Wales to assess the response of fishes to seagrass cover. We saw a clear positive relationship with the condition of P. australis; a high cover of this seagrass had positive effects on the diversity and abundance of cryptic fauna. Our findings highlight ecosystem shifts associated with the loss and fragmentation of biogenic habitat. These changes are of particular relevance for P. australis meadows given their current status as an endangered ecological community in several locations in NSW and their slow rate of recovery from disturbance. 相似文献
54.
Duncan Mortimer Marije Bosch Joanne E. Mckenzie Simon Turner Marisa Chau Jennie L. Ponsford Jonathan C. Knott Russell L. Gruen Sally E. Green 《Implementation science : IS》2018,13(1):147
Background
Evidence-based guidelines for the management of mild traumatic brain injury (mTBI) in the emergency department (ED) are now widely available, and yet, clinical practice remains inconsistent with the guidelines. The Neurotrauma Evidence Translation (NET) intervention was developed to increase the uptake of guideline recommendations and improve the management of minor head injury in Australian emergency departments (EDs). However, the adoption of this type of intervention typically entails an upfront investment that may or may not be fully offset by improvements in clinical practice, health outcomes and/or reductions in health service utilisation. The present study estimates the cost and cost-effectiveness of the NET intervention, as compared to the passive dissemination of the guideline, to evaluate whether any improvements in clinical practice or health outcomes due to the NET intervention can be obtained at an acceptable cost.Methods and findings
Study setting: The NET cluster randomised controlled trial [ACTRN12612001286831]. Study sample: Seventeen EDs were randomised to the control condition and 14 to the intervention. One thousand nine hundred forty-three patients were included in the analysis of clinical practice outcomes (NET sample). A total of 343 patients from 14 control and 10 intervention EDs participated in follow-up interviews and were included in the analysis of patient-reported health outcomes (NET-Plus sample). Outcome measures: Appropriate post-traumatic amnesia (PTA) screening in the ED (primary outcome). Secondary clinical practice outcomes: provision of written information on discharge (INFO) and safe discharge (defined as CT scan appropriately provided plus PTA plus INFO). Secondary patient-reported, post-discharge health outcomes: anxiety (Hospital Anxiety and Depression Scale), post-concussive symptoms (Rivermead), and preference-based health-related quality of life (SF6D). Methods: Trial-based economic evaluations from a health sector perspective, with time horizons set to coincide with the final follow-up for the NET sample (2 months post-intervention) and to 1-month post-discharge for the NET-Plus sample. Results: Intervention and control groups were not significantly different in health service utilisation received in the ED/inpatient ward following the initial mTBI presentation (adjusted mean difference $23.86 per patient; 95%CI ??$106, $153; p?=?0.719) or over the longer follow-up in the NET-plus sample (adjusted mean difference $341.78 per patient; 95%CI ??$58, $742; p?=?0.094). Savings from lower health service utilisation are therefore unlikely to offset the significantly higher upfront cost of the intervention (mean difference $138.20 per patient; 95%CI $135, $141; p?<?0.000). Estimates of the net effect of the intervention on total cost (intervention cost net of health service utilisation) suggest that the intervention entails significantly higher costs than the control condition (adjusted mean difference $169.89 per patient; 95%CI $43, $297, p?=?0.009). This effect is larger in absolute magnitude over the longer follow-up in the NET-plus sample (adjusted mean difference $505.06; 95%CI $96, $915; p?=?0.016), mostly due to additional health service utilisation. For the primary outcome, the NET intervention is more costly and more effective than passive dissemination; entailing an additional cost of $1246 per additional patient appropriately screened for PTA ($169.89/0.1363; Fieller’s 95%CI $525, $2055). For NET to be considered cost-effective with 95% confidence, decision-makers would need to be willing to trade one quality-adjusted life year (QALY) for 25 additional patients appropriately screened for PTA. While these results reflect our best estimate of cost-effectiveness given the data, it is possible that a NET intervention that has been scaled and streamlined ready for wider roll-out may be more or less cost-effective than the NET intervention as delivered in the trial.Conclusions
While the NET intervention does improve the management of mTBI in the ED, it also entails a significant increase in cost and—as delivered in the trial—is unlikely to be cost-effective at currently accepted funding thresholds. There may be a scope for a scaled-up and streamlined NET intervention to achieve a better balance between costs and outcomes.Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12612001286831, date registered 12 December 2012.55.
Identification of aminopyrimidine‐sulfonamides as potent modulators of Wag31‐mediated cell elongation in mycobacteria
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János Pató Gaëlle S. Kolly Jana Korduláková Martin Forbak Joanna C. Evans Rita Székely Jan Rybniker Zuzana Palčeková Júlia Zemanová Isabella Santi François Signorino‐Gelo Liliana Rodrigues Anthony Vocat Adrian S. Covarrubias Monica G. Rengifo Kai Johnsson Sherry Mowbray Joseph Buechler Vincent Delorme Priscille Brodin Graham W. Knott José A. Aínsa Digby F. Warner Katarína Mikušová John D. McKinney Ruben C. Hartkoorn 《Molecular microbiology》2017,103(1):13-25
56.
Wojciech Bobela Sameer Nazeeruddin Graham Knott Patrick Aebischer Bernard L. Schneider 《Molecular neurodegeneration》2017,12(1):80
Background
Metabolic perturbations and slower renewal of cellular components associated with aging increase the risk of Parkinson’s disease (PD). Declining activity of AMPK, a critical cellular energy sensor, may therefore contribute to neurodegeneration.Methods
Here, we overexpress various genetic variants of the catalytic AMPKα subunit to determine how AMPK activity affects the survival and function of neurons overexpressing human α-synuclein in vivo.Results
Both AMPKα1 and α2 subunits have neuroprotective effects against human α-synuclein toxicity in nigral dopaminergic neurons. Remarkably, a modified variant of AMPKα1 (T172Dα1) with constitutive low activity most effectively prevents the loss of dopamine neurons, as well as the motor impairments caused by α-synuclein accumulation. In the striatum, T172Dα1 decreases the formation of dystrophic axons, which contain aggregated α-synuclein. In primary cortical neurons, overexpression of human α-synuclein perturbs mitochondrial and lysosomal activities. Co-expressing AMPKα with α-synuclein induces compensatory changes, which limit the accumulation of lysosomal material and increase the mitochondrial mass.Conclusions
Together, these results indicate that modulating AMPK activity can mitigate α-synuclein toxicity in nigral dopamine neurons, which may have implications for the development of neuroprotective treatments against PD.57.
Seasonal genetic variation associated with population dynamics of a poecilogonous polychaete worm
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Anne Thonig Gary Thomas Banta Benni Winding Hansen K. Emily Knott 《Ecology and evolution》2017,7(23):10005-10017
Poecilogonous species show variation in developmental mode, with larvae that differ both morphologically and ecologically. The spionid polychaete Pygospio elegans shows variation in developmental mode not only between populations, but also seasonally within populations. We investigated the consequences of this developmental polymorphism on the spatial and seasonal genetic structure of P. elegans at four sites in the Danish Isefjord‐Roskilde‐Fjord estuary at six time points, from March 2014 until February 2015. We found genetic differentiation between our sampling sites as well as seasonal differentiation at two of the sites. The seasonal genetic shift correlated with the appearance of new size cohorts in the populations. Additionally, we found that the genetic composition of reproductive individuals did not always reflect the genetic composition of the entire sample, indicating that variance in reproductive success among individuals is a likely explanation for the patterns of chaotic genetic patchiness observed during this and previous studies. The heterogeneous, unpredictable character of the estuary might maintain poecilogony in P. elegans as a bet‐hedging strategy in the Isefjord‐Roskilde‐Fjord complex in comparison with other sites where P. elegans are expected to be fixed to a certain mode of development. 相似文献
58.
Mitochondria are remarkably dynamic organelles that migrate, divide and fuse. Cycles of mitochondrial fission and fusion ensure metabolite and mitochondrial DNA mixing and dictate organelle shape, number and bioenergetic functionality. There is mounting evidence that mitochondrial dysfunction is an early and causal event in neurodegeneration. Mutations in the mitochondrial fusion GTPases mitofusin 2 and optic atrophy 1, neurotoxins and oxidative stress all disrupt the cable-like morphology of functional mitochondria. This results in impaired bioenergetics and mitochondrial migration, and can trigger neurodegeneration. These findings suggest potential new treatment avenues for neurodegenerative diseases. 相似文献
59.
60.
Variation in and amplification conditions for nine polymorphic microsatellite loci identified from Lymnaea stagnalis, a hermaphroditic pulmonate snail, are described. Eight populations from central Finland were studied, which varied in terms of both observed polymorphism and heterozygosity. The number of alleles at each locus is moderate (two to seven), except for one exceptional locus having 16 alleles, and for which null alleles are possible. There is no evidence for genotypic disequilibrium in the populations for all pairs of loci. Heterozygosity levels are indicative of outcrossing in L. stagnalis, whose mating system will be characterized further using these markers. 相似文献