全文获取类型
收费全文 | 607篇 |
免费 | 52篇 |
出版年
2023年 | 3篇 |
2022年 | 1篇 |
2021年 | 13篇 |
2020年 | 4篇 |
2019年 | 11篇 |
2018年 | 16篇 |
2017年 | 11篇 |
2016年 | 22篇 |
2015年 | 30篇 |
2014年 | 31篇 |
2013年 | 44篇 |
2012年 | 48篇 |
2011年 | 62篇 |
2010年 | 35篇 |
2009年 | 33篇 |
2008年 | 40篇 |
2007年 | 40篇 |
2006年 | 27篇 |
2005年 | 28篇 |
2004年 | 23篇 |
2003年 | 21篇 |
2002年 | 29篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 11篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 7篇 |
1984年 | 1篇 |
1978年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有659条查询结果,搜索用时 171 毫秒
91.
92.
Via E Cardoner N Pujol J Martínez-Zalacaín I Hernández-Ribas R Urretavizacaya M López-Solà M Deus J Menchón JM Soriano-Mas C 《PloS one》2012,7(6):e38299
Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF) spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm ('new segment', as implemented in the software Statistical Parametric Mapping-SPM8), incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI) was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the 'new segment' algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the 'unified segmentation' approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the 'unified segmentation' approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches. The reliable characterization of CSF alterations may help in the comprehensive characterization of brain structural abnormalities in psychiatric samples and in the development of etiopathogenic hypotheses relating to the disorders. 相似文献
93.
Alternative splicing is the mechanism by which different combinations of exons in the pre-mRNA give rise to distinct mature mRNAs. This process is mediated by splicing factors that bind the pre-mRNA and affect the recognition of its splicing signals. Saccharomyces species lack many of the regulatory factors present in metazoans. Accordingly, it is generally assumed that the amount of alternative splicing is limited. However, there is recent compelling evidence that yeast have functional alternative splicing, mainly in response to environmental conditions. We have previously shown that sequence and structure properties of the pre-mRNA could explain the selection of 3' splice sites (ss) in Saccharomyces cerevisiae. In this work, we extend our previous observations to build a computational classifier that explains most of the annotated 3'ss in the CDS and 5' UTR of this organism. Moreover, we show that the same rules can explain the selection of alternative 3'ss. Experimental validation of a number of predicted alternative 3'ss shows that their usage is low compared to annotated 3'ss. The majority of these alternative 3'ss introduce premature termination codons (PTCs), suggesting a role in expression regulation. Furthermore, a genome-wide analysis of the effect of temperature, followed by experimental validation, yields only a small number of changes, indicating that this type of regulation is not widespread. Our results are consistent with the presence of alternative 3'ss selection in yeast mediated by the pre-mRNA structure, which can be responsive to external cues, like temperature, and is possibly related to the control of gene expression. 相似文献
94.
The present study examined the use of foreknowledge in a task-cueing protocol while manipulating sensory updating and executive control in both, informatively and non-informatively pre-cued trials. Foreknowledge, sensory updating (cue switch effects) and task-switching were orthogonally manipulated in order to address the question of whether, and to which extent, the sensory processing of cue changes can partly or totally explain the final task switch costs. Participants responded faster when they could prepare for the upcoming task and if no task-set updating was necessary. Sensory cue switches influenced cue-locked ERPs only when they contained conceptual information about the upcoming task: frontal P2 amplitudes were modulated by task-relevant cue changes, mid-parietal P3 amplitudes by the anticipatory updating of stimulus-response mappings, and P3 peak latencies were modulated by task switching. Task preparation was advantageous for efficient stimulus-response re-mapping at target-onset as mirrored in target N2 amplitudes. However, N2 peak latencies indicate that this process is faster for all repeat trials. The results provide evidence to support a very fast detection of task-relevance in sensory (cue) changes and argue against the view of task repetition benefits as secondary to purely perceptual repetition priming. Advanced preparation may have a stronger influence on behavioral performance and target-locked brain activity than the local effect of repeating or switching the task-set in the current trial. 相似文献
95.
96.
Marcello A. Mannino Giulio Catalano Sahra Talamo Giovanni Mannino Rosaria Di Salvo Vittoria Schimmenti Carles Lalueza-Fox Andrea Messina Daria Petruso David Caramelli Michael P. Richards Luca Sineo 《PloS one》2012,7(11)
Hunter-gatherers living in Europe during the transition from the late Pleistocene to the Holocene intensified food acquisition by broadening the range of resources exploited to include marine taxa. However, little is known on the nature of this dietary change in the Mediterranean Basin. A key area to investigate this issue is the archipelago of the Ègadi Islands, most of which were connected to Sicily until the early Holocene. The site of Grotta d’Oriente, on the present-day island of Favignana, was occupied by hunter-gatherers when Postglacial environmental changes were taking place (14,000-7,500 cal BP). Here we present the results of AMS radiocarbon dating, palaeogenetic and isotopic analyses undertaken on skeletal remains of the humans buried at Grotta d’Oriente. Analyses of the mitochondrial hypervariable first region of individual Oriente B, which belongs to the HV-1 haplogroup, suggest for the first time on genetic grounds that humans living in Sicily during the early Holocene could have originated from groups that migrated from the Italian Peninsula around the Last Glacial Maximum. Carbon and nitrogen isotope analyses show that the Upper Palaeolithic and Mesolithic hunter-gatherers of Favignana consumed almost exclusively protein from terrestrial game and that there was only a slight increase in marine food consumption from the late Pleistocene to the early Holocene. This dietary change was similar in scale to that at sites on mainland Sicily and in the rest of the Mediterranean, suggesting that the hunter-gatherers of Grotta d’Oriente did not modify their subsistence strategies specifically to adapt to the progressive isolation of Favignana. The limited development of technologies for intensively exploiting marine resources was probably a consequence both of Mediterranean oligotrophy and of the small effective population size of these increasingly isolated human groups, which made innovation less likely and prevented transmission of fitness-enhancing adaptations. 相似文献
97.
Jussi Pihlajamäki Carles Lerin Dorota Kaminska Sari Venesmaa Paula Itkonen Tanner Boes Thomas Floss Joshua Schroeder Farrell Dearie Sarah Crunkhorn Furkan Burak Josep C. Jimenez-Chillaron Tiina Kuulasmaa Pekka Miettinen Peter J. Park Imad Nasser Zhenwen Zhao Zhaiyi Zhang Yan Xu Wolfgang Wurst Mary Elizabeth Patti 《Cell metabolism》2012,15(3):267-269
98.
Rentero C Zech T Quinn CM Engelhardt K Williamson D Grewal T Jessup W Harder T Gaus K 《PloS one》2008,3(5):e2262
The T lymphocyte plasma membrane condenses at the site of activation but the functional significance of this receptor-mediated membrane reorganization is not yet known. Here we demonstrate that membrane condensation at the T cell activation sites can be inhibited by incorporation of the oxysterol 7-ketocholesterol (7KC), which is known to prevent the formation of raft-like liquid-ordered domains in model membranes. We enriched T cells with 7KC, or cholesterol as control, to assess the importance of membrane condensation for T cell activation. Upon 7KC treatment, T cell antigen receptor (TCR) triggered calcium fluxes and early tyrosine phosphorylation events appear unaltered. However, signaling complexes form less efficiently on the cell surface, fewer phosphorylated signaling proteins are retained in the plasma membrane and actin restructuring at activation sites is impaired in 7KC-enriched cells resulting in compromised downstream activation responses. Our data emphasizes lipids as an important medium for the organization at T cell activation sites and strongly indicates that membrane condensation is an important element of the T cell activation process. 相似文献
99.
Cifuentes D Martínez-Pons C García-Rocha M Galina A Ribas de Pouplana L Guinovart JJ 《The Journal of biological chemistry》2008,283(9):5642-5649
Glucokinase (GK, hexokinase type IV) is required for the accumulation of glycogen in adult liver and hepatoma cells. Paradoxically, mammalian embryonic livers store glycogen successfully in the absence of GK. Here we address how mammalian embryonic livers, but not adult livers or hepatoma cells, manage to accumulate glycogen in the absence of this enzyme. Hexokinase type I or II (HKI, HKII) substitutes for GK in hepatomas and in embryonic livers. We engineered FTO2B cells, a hepatoma cell line in which GK is not expressed, to unveil the modifications required to allow them to accumulate glycogen. In the light of these results, we then examined glycogen metabolism in embryonic liver. Glycogen accumulation in FTO2B cells can be triggered through elevated expression of HKI or either of the protein phosphatase 1 regulatory subunits, namely PTG or G L. Between these two strategies to activate glycogen deposition in the absence of GK, embryonic livers choose to express massive levels of HKI and HKII. We conclude that although the GK/liver glycogen synthase tandem is ideally suited to store glycogen in liver when blood glucose is high, the substitution of HKI for GK in embryonic livers allows the HKI/liver glycogen synthase tandem to make glycogen independently of the glucose concentration in blood, although it requires huge levels of HK. Moreover, the physiological consequence of the HK isoform switch is that the embryonic liver safeguards its glycogen deposits, required as the main source of energy at birth, from maternal starvation. 相似文献
100.
Carles M. Gasol Ramon Farreny Xavier Gabarrell Joan Rieradevall 《The International Journal of Life Cycle Assessment》2008,13(5):421-431
Goal, scope and background The industrial packages sector has great importance for the transport sector in Europe. These containers, mainly wooden pallets
and spools, are subject to European legislation, which promotes their reuse and recycling. This study uses life cycle assessment
(LCA) to assess the environmental impact of the current management system in this sector and the benefits and drawbacks of
different reuse intensities as a waste prevention strategy as opposed to the recycling option.
Materials and methods In this paper, four case studies located in Spain and representative of the wooden package sector in Europe are analysed:
high reuse pallet, low reuse pallet, low reuse spool and null reuse spool. For the LCA study cases, the functional unit is
that required to satisfy the transport necessity of 1,000 t by road. The impact and energy consumption assessment methods
used are CML 2 Baseline 2000 and Cumulative Energy Demand. Data are mostly provided by the leading enterprises and organisations
in this sector.
Results The paper provides, as a first result, a comprehensive inventory of the systems under study. Secondly, our assessment shows
that the systems with higher reuse intensity show a reduction in energy and wood consumption and all the environmental impact
categories except for the global warming potential from 34.0% to 81.0% in the pallet study cases and from 50.4% to 72.8% in
the spool ones. This reduction is at the expense of the maintenance stage, which on the contrary increases its impact, although
it is still relatively small—less than 7% in all the impact categories and flow indicators of the study cases. The highest
impact stages are transport, raw material extraction and the process chain. The final disposal and maintenance stages are
the lowest impact, contributing at most to less than 30% of the impact in the pallet study cases and 10% in the spool cases.
Discussion Wood consumption (WC), directly related to the number of containers needed to satisfy the functional unit, is the main factor
in determining the impact of the stages, especially in the raw materials extraction and process chain stages, assuming that
these are undertaken with the same technologies in all the case studies. Other variables, such as the management system, the
maintenance index and the final disposal scenario, affect the impact of the remaining stages: transport, maintenance and final
disposal. The global warming potential results obtained demonstrate the environmental benefits of using containers made of
a renewable resource such as wood instead of using other materials, but these results are not expected to prioritise the lower
reuse systems because of their better performance in this category.
Conclusions Reuse, a strategy capable of reducing the environmental impacts of the wooden container systems, is preferable to recycling,
while the package maintenance tasks are still feasible. Therefore, reuse, combined with recycling as final disposal, should
be encouraged to reduce the demand for natural resources and the waste generated.
Recommendations Based on these results, attention should be paid to the maintenance stage, which, being the lowest-impact one, could substantially
reduce the impact of the remaining stages. 相似文献