全文获取类型
收费全文 | 6743篇 |
免费 | 527篇 |
国内免费 | 1篇 |
专业分类
7271篇 |
出版年
2023年 | 42篇 |
2022年 | 116篇 |
2021年 | 192篇 |
2020年 | 118篇 |
2019年 | 132篇 |
2018年 | 155篇 |
2017年 | 124篇 |
2016年 | 218篇 |
2015年 | 394篇 |
2014年 | 421篇 |
2013年 | 494篇 |
2012年 | 624篇 |
2011年 | 559篇 |
2010年 | 367篇 |
2009年 | 353篇 |
2008年 | 456篇 |
2007年 | 416篇 |
2006年 | 358篇 |
2005年 | 300篇 |
2004年 | 266篇 |
2003年 | 288篇 |
2002年 | 258篇 |
2001年 | 50篇 |
2000年 | 36篇 |
1999年 | 65篇 |
1998年 | 50篇 |
1997年 | 46篇 |
1996年 | 27篇 |
1995年 | 35篇 |
1994年 | 36篇 |
1993年 | 31篇 |
1992年 | 28篇 |
1991年 | 17篇 |
1990年 | 8篇 |
1989年 | 12篇 |
1988年 | 19篇 |
1987年 | 7篇 |
1986年 | 11篇 |
1985年 | 5篇 |
1984年 | 10篇 |
1983年 | 7篇 |
1982年 | 10篇 |
1981年 | 6篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1974年 | 9篇 |
1973年 | 5篇 |
1970年 | 5篇 |
1969年 | 8篇 |
排序方式: 共有7271条查询结果,搜索用时 15 毫秒
61.
Paradis C Cloutier P Shkreta L Toutant J Klarskov K Chabot B 《RNA (New York, N.Y.)》2007,13(8):1287-1300
The control of alternative pre-mRNA splicing often requires the participation of factors displaying synergistic or antagonistic activities. In the hnRNP A1 pre-mRNA, three elements promote the exclusion of alternative exon 7B, while a fourth intron element (CE9) represses splicing of exon 7B to the downstream exon. We have shown previously that the 5' portion of the 38-nucleotide-long CE9 element is bound by SRp30c, and that this interaction is important for repression in vitro. To determine whether SRp30c alone can impose repression, we tested a high-affinity SRp30c binding site that we identified using the SELEX protocol. We find that multiple high-affinity SRp30c sites are required to replicate the level of repression obtained with CE9, and that both the 5' and the 3' portions of CE9 contribute to SRp30c binding. Performing RNA affinity chromatography with the complete CE9 element recovered hnRNP I/PTB. Surprisingly however, His-tagged PTB reduced the binding of SRp30c to CE9 in a nuclear extract, stimulated splicing to a downstream 3' splice site, and relieved the CE9-mediated splicing repression in vitro. Our in vivo results are consistent with the notion that increasing PTB levels alleviates the repression imposed by CE9 to a downstream 3' splice site. Thus, PTB can function as an anti-repressor molecule to counteract the splicing inhibitory activity of SRp30c. 相似文献
62.
Heroen Verbruggen † Lennert Tyberghein † Klaas Pauly † Caroline Vlaeminck Katrien Van Nieuwenhuyze Wiebe H.C.F. Kooistra Frederik Leliaert Olivier De Clerck 《Global Ecology and Biogeography》2009,18(4):393-405
Aim Because of their broad distribution in geographical and ecological dimensions, seaweeds (marine macroalgae) offer great potential as models for marine biogeographical inquiry and exploration of the interface between macroecology and macroevolution. This study aims to characterize evolutionary niche dynamics in the common green seaweed genus Halimeda, use the observed insights to gain understanding of the biogeographical history of the genus and predict habitats that can be targeted for the discovery of species of special biogeographical interest. Location Tropical and subtropical coastal waters. Methods The evolutionary history of the genus is characterized using molecular phylogenetics and relaxed molecular clock analysis. Niche modelling is carried out with maximum entropy techniques and uses macroecological data derived from global satellite imagery. Evolutionary niche dynamics are inferred through application of ancestral character state estimation. Results A nearly comprehensive molecular phylogeny of the genus was inferred from a six‐locus dataset. Macroecological niche models showed that species distribution ranges are considerably smaller than their potential ranges. We show strong phylogenetic signal in various macroecological niche features. Main conclusions The evolution of Halimeda is characterized by conservatism for tropical, nutrient‐depleted habitats, yet one section of the genus managed to invade colder habitats multiple times independently. Niche models indicate that the restricted geographical ranges of Halimeda species are not due to habitat unsuitability, strengthening the case for dispersal limitation. Niche models identified hotspots of habitat suitability of Caribbean species in the eastern Pacific Ocean. We propose that these hotspots be targeted for discovery of new species separated from their Caribbean siblings since the Pliocene rise of the Central American Isthmus. 相似文献
63.
Petitdemange C Becquart P Wauquier N Béziat V Debré P Leroy EM Vieillard V 《PLoS pathogens》2011,7(9):e1002268
Chikungunya virus (CHIKV) is a worldwide emerging pathogen. In humans it causes a syndrome characterized by high fever, polyarthritis, and in some cases lethal encephalitis. Growing evidence indicates that the innate immune response plays a role in controlling CHIKV infection. We show here that CHIKV induces major but transient modifications in NK-cell phenotype and function soon after the onset of acute infection. We report a transient clonal expansion of NK cells that coexpress CD94/NKG2C and inhibitory receptors for HLA-C1 alleles and are correlated with the viral load. Functional tests reveal cytolytic capacity driven by NK cells in the absence of exogenous signals and severely impaired IFN-γ production. Collectively these data provide insight into the role of this unique subset of NK cells in controlling CHIKV infection by subset-specific expansion in response to acute infection, followed by a contraction phase after viral clearance. 相似文献
64.
Caroline J. Rose Katrin Hammerschmidt Yuriy Pichugin Paul B. Rainey 《Ecology letters》2020,23(9):1380-1390
The evolutionary transition to multicellularity has occurred on numerous occasions, but transitions to complex life forms are rare. Here, using experimental bacterial populations as proxies for nascent multicellular organisms, we manipulate ecological factors shaping the evolution of groups. Groups were propagated under regimes requiring reproduction via a life cycle replete with developmental and dispersal (propagule) phases, but in one treatment lineages never mixed, whereas in a second treatment, cells from different lineages experienced intense competition during the dispersal phase. The latter treatment favoured traits promoting cell growth at the expense of traits underlying group fitness – a finding that is supported by results from a mathematical model. Our results show that the transition to multicellularity benefits from ecological conditions that maintain discreteness not just of the group (soma) phase, but also of the dispersal (germline) phase. 相似文献
65.
66.
Rob C. van Lummel Stefan Walgaard Markus A. Hobert Walter Maetzler Jaap H. van Die?n Francisca Galindo-Garre Caroline B. Terwee 《PloS one》2016,11(3)
Background
The “Timed Up and Go” (TUG) is a widely used measure of physical functioning in older people and in neurological populations, including Parkinson’s Disease. When using an inertial sensor measurement system (instrumented TUG [iTUG]), the individual components of the iTUG and the trunk kinematics can be measured separately, which may provide relevant additional information.Objective
The aim of this study was to determine intra-rater, inter-rater and test-retest reliability of the iTUG in patients with Parkinson’s Disease.Methods
Twenty eight PD patients, aged 50 years or older, were included. For the iTUG the DynaPort Hybrid (McRoberts, The Hague, The Netherlands) was worn at the lower back. The device measured acceleration and angular velocity in three directions at a rate of 100 samples/s. Patients performed the iTUG five times on two consecutive days. Repeated measurements by the same rater on the same day were used to calculate intra-rater reliability. Repeated measurements by different raters on the same day were used to calculate intra-rater and inter-rater reliability. Repeated measurements by the same rater on different days were used to calculate test-retest reliability.Results
Nineteen ICC values (15%) were ≥ 0.9 which is considered as excellent reliability. Sixty four ICC values (49%) were ≥ 0.70 and < 0.90 which is considered as good reliability. Thirty one ICC values (24%) were ≥ 0.50 and < 0.70, indicating moderate reliability. Sixteen ICC values (12%) were ≥ 0.30 and < 0.50 indicating poor reliability. Two ICT values (2%) were < 0.30 indicating very poor reliability.Conclusions
In conclusion, in patients with Parkinson’s disease the intra-rater, inter-rater, and test-retest reliability of the individual components of the instrumented TUG (iTUG) was excellent to good for total duration and for turning durations, and good to low for the sub durations and for the kinematics of the SiSt and StSi. The results of this fully automated analysis of instrumented TUG movements demonstrate that several reliable TUG parameters can be identified that provide a basis for a more precise, quantitative use of the TUG test, in clinical practice. 相似文献67.
Juxing Chen Jinzhi Wang Kathrin R. Meyers Caroline A. Enns 《Traffic (Copenhagen, Denmark)》2009,10(10):1488-1501
Transferrin receptor 2 (TfR2) is a homologue of transferrin receptor 1 (TfR1) but has distinct functions from TfR1 in iron homeostasis. In keeping with its proposed role in iron sensing, previous studies showed that TfR2 has a short half-life and that holo-Tf stabilizes TfR2 by redirecting it from a degradative pathway to a recycling pathway. In this study, we characterized how the endocytosis, recycling and degradation of TfR2 relates to its function and differs from TfR1. TfR2 endocytosis was adaptor protein-2 (AP-2) dependent. Flow cytometry analysis showed that TfR1 and TfR2 utilized the same endocytic pathway only in the presence of holo-Tf, indicating that holo-Tf alters the interaction of TfR2 with the endocytic machinery. Unlike TfR1, phosphofurin acidic cluster sorting protein 1 (PACS-1) binds to the cytoplasmic domain of TfR2 and data suggest that PACS-1 is involved in the TfR2 recycling. Depletion of TSG101 by siRNA or expression of a dominant negative Vps4 inhibited TfR2 degradation, indicating that TfR2 degradation occurs through a multivesicular body (MVB) pathway. TfR2 degradation is not mediated through ubiquitination on the single lysine (K31) in the cytoplasmic domain or on the amino terminal residue. No ubiquitination of TfR2 by HA-ubiquitin was detected, indicating a lack of direct TfR2 ubiquitination involvement in its degradation. 相似文献
68.
Synaptic destabilization by neuronal Nogo-A 总被引:1,自引:0,他引:1
Aloy EM Weinmann O Pot C Kasper H Dodd DA Rülicke T Rossi F Schwab ME 《Brain Cell Biology》2006,35(2-3):137-157
Formation and maintenance of a neuronal network is based on a balance between plasticity and stability of synaptic connections.
Several molecules have been found to regulate the maintenance of excitatory synapses but nothing is known about the molecular
mechanisms involved in synaptic stabilization versus disassembly at inhibitory synapses. Here, we demonstrate that Nogo-A,
which is well known to be present in myelin and inhibit growth in the adult CNS, is present in inhibitory presynaptic terminals
in cerebellar Purkinje cells at the time of Purkinje cell-Deep Cerebellar Nuclei (DCN) inhibitory synapse formation and is
then downregulated during synapse maturation. We addressed the role of neuronal Nogo-A in synapse maturation by generating
several mouse lines overexpressing Nogo-A, starting at postnatal ages and throughout adult life, specifically in cerebellar
Purkinje cells and their terminals. The overexpression of Nogo-A induced a progressive disassembly, retraction and loss of
the inhibitory Purkinje cell terminals. This led to deficits in motor learning and coordination in the transgenic mice. Prior
to synapse disassembly, the overexpression of neuronal Nogo-A led to the downregulation of the synaptic scaffold proteins
spectrin, spectrin-E and β-catenin in the postsynaptic neurons. Our data suggest that neuronal Nogo-A might play a role in
the maintenance of inhibitory synapses by modulating the expression of synaptic anchoring molecules.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
69.
Anaerobic Granular Sludge Bioreactor Technology 总被引:1,自引:0,他引:1
McHugh Sharon O'Reilly Caroline Mahony Thérèse Colleran Emer O'Flaherty Vincent 《Reviews in Environmental Science and Biotechnology》2003,2(2-4):225-245
Anaerobic digestion is a mature wastewater treatment technology, with worldwide application. The predominantly applied bioreactor designs, such as the upflow anaerobic sludge blanket and expanded granular sludge bed, are based on the spontaneous formation of granular sludge. Despite the exploitation of granular reactors at full-scale for more than two decades, the mechanisms of granulation are not completely understood and numerous theories have been put forward to describe the process from a biological, ecological and engineering point of view. New technological opportunities are emerging for anaerobic digestion, aided by an improved understanding of microbiological and environmental factors affecting the formation and activity of anaerobic granular sludge. 相似文献
70.
James D. Glover Lorna Taylor Adrian Sherman Caroline Zeiger-Poli Helen M. Sang Michael J. McGrew 《PloS one》2013,8(11)
In this work, we describe a single piggyBac transposon system containing both a tet-activator and a doxycycline-inducible expression cassette. We demonstrate that a gene product can be conditionally expressed from the integrated transposon and a second gene can be simultaneously targeted by a short hairpin RNA contained within the transposon, both in vivo and in mammalian and avian cell lines. We applied this system to stably modify chicken primordial germ cell (PGC) lines in vitro and induce a reporter gene at specific developmental stages after injection of the transposon-modified germ cells into chicken embryos. We used this vector to express a constitutively-active AKT molecule during PGC migration to the forming gonad. We found that PGC migration was retarded and cells could not colonise the forming gonad. Correct levels of AKT activation are thus essential for germ cell migration during early embryonic development. 相似文献