全文获取类型
收费全文 | 511篇 |
免费 | 80篇 |
国内免费 | 2篇 |
出版年
2022年 | 4篇 |
2021年 | 11篇 |
2020年 | 7篇 |
2019年 | 7篇 |
2018年 | 7篇 |
2017年 | 7篇 |
2016年 | 7篇 |
2015年 | 21篇 |
2014年 | 17篇 |
2013年 | 19篇 |
2012年 | 21篇 |
2011年 | 27篇 |
2010年 | 29篇 |
2009年 | 25篇 |
2008年 | 18篇 |
2007年 | 18篇 |
2006年 | 12篇 |
2005年 | 21篇 |
2004年 | 12篇 |
2003年 | 15篇 |
2002年 | 13篇 |
2001年 | 7篇 |
2000年 | 10篇 |
1999年 | 13篇 |
1998年 | 9篇 |
1997年 | 15篇 |
1996年 | 10篇 |
1995年 | 4篇 |
1994年 | 8篇 |
1993年 | 10篇 |
1992年 | 10篇 |
1991年 | 16篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 10篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 8篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1953年 | 3篇 |
1946年 | 3篇 |
排序方式: 共有593条查询结果,搜索用时 15 毫秒
151.
Golczak M Kiser PD Sears AE Lodowski DT Blaner WS Palczewski K 《The Journal of biological chemistry》2012,287(28):23790-23807
Lecithin:retinol acyltransferase-like proteins, also referred to as HRAS-like tumor suppressors, comprise a vertebrate subfamily of papain-like or NlpC/P60 thiol proteases that function as phospholipid-metabolizing enzymes. HRAS-like tumor suppressor 3, a representative member of this group, plays a key role in regulating triglyceride accumulation and energy expenditure in adipocytes and therefore constitutes a novel pharmacological target for treatment of metabolic disorders causing obesity. Here, we delineate a catalytic mechanism common to lecithin:retinol acyltransferase-like proteins and provide evidence for their alternative robust lipid-dependent acyltransferase enzymatic activity. We also determined high resolution crystal structures of HRAS-like tumor suppressor 2 and 3 to gain insight into their active site architecture. Based on this structural analysis, two conformational states of the catalytic Cys-113 were identified that differ in reactivity and thus could define the catalytic properties of these two proteins. Finally, these structures provide a model for the topology of these enzymes and allow identification of the protein-lipid bilayer interface. This study contributes to the enzymatic and structural understanding of HRAS-like tumor suppressor enzymes. 相似文献
152.
Xiaobo Li Eric R. Moellering Bensheng Liu Cassandra Johnny Marie Fedewa Barbara B. Sears Min-Hao Kuo Christoph Benning 《The Plant cell》2012,24(11):4670-4686
Following N deprivation, microalgae accumulate triacylglycerols (TAGs). To gain mechanistic insights into this phenomenon, we identified mutants with reduced TAG content following N deprivation in the model alga Chlamydomonas reinhardtii. In one of the mutants, the disruption of a galactoglycerolipid lipase-encoding gene, designated PLASTID GALACTOGLYCEROLIPID DEGRADATION1 (PGD1), was responsible for the primary phenotype: reduced TAG content, altered TAG composition, and reduced galactoglycerolipid turnover. The recombinant PGD1 protein, which was purified from Escherichia coli extracts, hydrolyzed monogalactosyldiacylglycerol into its lyso-lipid derivative. In vivo pulse-chase labeling identified galactoglycerolipid pools as a major source of fatty acids esterified in TAGs following N deprivation. Moreover, the fatty acid flux from plastid lipids to TAG was decreased in the pgd1 mutant. Apparently, de novo–synthesized fatty acids in Chlamydomonas
reinhardtii are, at least partially, first incorporated into plastid lipids before they enter TAG synthesis. As a secondary effect, the pgd1 mutant exhibited a loss of viability following N deprivation, which could be avoided by blocking photosynthetic electron transport. Thus, the pgd1 mutant provides evidence for an important biological function of TAG synthesis following N deprivation, namely, relieving a detrimental overreduction of the photosynthetic electron transport chain. 相似文献
153.
Protein phosphatase 2A regulatory subunit B56alpha associates with c-myc and negatively regulates c-myc accumulation 总被引:1,自引:0,他引:1 下载免费PDF全文
Protein phosphatase 2A (PP2A) plays a prominent role in controlling accumulation of the proto-oncoprotein c-Myc. PP2A mediates its effects on c-Myc by dephosphorylating a conserved residue that normally stabilizes c-Myc, and in this way, PP2A enhances c-Myc ubiquitin-mediated degradation. Stringent regulation of c-Myc levels is essential for normal cell function, as c-Myc overexpression can lead to cell transformation. Conversely, PP2A has tumor suppressor activity. Uncovering relevant PP2A holoenzymes for a particular target has been limited by the fact that cellular PP2A represents a large heterogeneous population of trimeric holoenzymes, composed of a conserved catalytic subunit and a structural subunit along with a variable regulatory subunit which directs the holoenzyme to a specific target. We now report the identification of a specific PP2A regulatory subunit, B56alpha, that selectively associates with the N terminus of c-Myc. B56alpha directs intact PP2A holoenzymes to c-Myc, resulting in a dramatic reduction in c-Myc levels. Inhibition of PP2A-B56alpha holoenzymes, using small hairpin RNA to knock down B56alpha, results in c-Myc overexpression, elevated levels of c-Myc serine 62 phosphorylation, and increased c-Myc function. These results uncover a new protein involved in regulating c-Myc expression and reveal a critical interconnection between a potent oncoprotein, c-Myc, and a well-documented tumor suppressor, PP2A. 相似文献
154.
Setting the record straight: a rebuttal to an erroneous analysis on transgenic insecticidal crops and natural enemies 总被引:2,自引:0,他引:2
155.
Estate Sokhadze Joshua Baruth Allan Tasman Lonnie Sears Grace Mathai Ayman El-Baz Manuel F. Casanova 《Applied psychophysiology and biofeedback》2009,34(1):37-51
To better understand visual processing abnormalities in autism we studied the attention orienting related frontal event potentials
(ERP) and the sustained attention related centro-parietal ERPs in a three stimulus oddball experiment. The three stimulus
oddball paradigm was aimed to test the hypothesis that individuals with autism abnormally orient their attention to novel
distracters as compared to controls. A dense-array 128 channel EGI electroencephalographic (EEG) system was used on 11 high-functioning
children and young adults with autism spectrum disorder (ASD) and 11 age-matched, typically developing control subjects. Patients
with ASD showed slower reaction times but did not differ in response accuracy. At the anterior (frontal) topography the ASD
group showed significantly higher amplitudes and longer latencies of early ERP components (e.g., P100, N100) to novel distracter
stimuli in both hemispheres. The ASD group also showed prolonged latencies of late ERP components (e.g., P2a, N200, P3a) to
novel distracter stimuli in both hemispheres. However, differences were more profound in the right hemisphere for both early
and late ERP components. Our results indicate augmented and prolonged early frontal potentials and a delayed P3a component
to novel stimuli, which suggest low selectivity in pre-processing and later-stage under-activation of integrative regions
in the prefrontal cortices. Also, at the posterior (centro-parietal) topography the ASD group showed significantly prolonged
N100 latencies and reduced amplitudes of the N2b component to target stimuli. In addition, the latency of the P3b component
was prolonged to novel distracters in the ASD group. In general, the autistic group showed prolonged latencies to novel stimuli
especially in the right hemisphere. These results suggest that individuals with autism over-process information needed for
the successful differentiation of target and novel stimuli. We propose the potential application of ERP evaluations in a novelty
task as outcome measurements in the biobehavioral treatment (e.g., EEG biofeedback, TMS) of autism. 相似文献
156.
Tomsheck AR Strobel GA Booth E Geary B Spakowicz D Knighton B Floerchinger C Sears J Liarzi O Ezra D 《Microbial ecology》2010,60(4):903-914
An endophytic fungus of Persea indica was identified, on the basis of its anamorphic stage, as Nodulosporium sp. by SEM. Partial sequence analysis of ITS rDNA revealed the identity of the teleomorphic stage of the fungus as Hypoxylon sp. It produces an impressive spectrum of volatile organic compounds (VOCs), most notably 1,8-cineole, 1-methyl-1,4-cyclohexadiene, and tentatively identified (+)-.alpha.-methylene-.alpha.-fenchocamphorone, among many others, most of which are unidentified. Six-day-old cultures of Hypoxylon sp. displayed maximal VOC-antimicrobial activity against Botrytis cinerea, Phytophthora cinnamomi, Cercospora beticola, and Sclerotinia sclerotiorum suggesting that the VOCs may play some role in the biology of the fungus and its survival in its host plant. Media containing starch- or sugar-related substrates best supported VOC production by the fungus. Direct on-line quantification of VOCs was measured by proton transfer mass spectrometry covering a continuous range with optimum VOC production occurred at 6 days at 145 ppmv with a rate of production of 7.65 ppmv/h. This report unequivocally demonstrates that 1,8-cineole (a monoterpene) is produced by a microorganism, which represents a novel and important source of this compound. This monoterpene is an octane derivative and has potential use as a fuel additive as do the other VOCs of this organism. Thus, fungal sourcing of this compound and other VOCs as produced by Hypoxylon sp. greatly expands their potential applications in medicine, industry, and energy production. 相似文献
157.
Abstract: We present the first record of the cardiid genus Monodacna from the Pliocene of Anatolia, Turkey. Monodacna imrei sp. nov. was found in the Pliocene Killik Formation from the western margin of the Baklan Basin, in very marginal brackish to freshwater lacustrine deposits. The new record extends the stratigraphic range of the modern Ponto‐Caspian genus back into the Pliocene and adds to earlier evidence that modern Ponto‐Caspian taxa originated in the Pliocene of south‐western Turkey. 相似文献
158.
A. SOTO J. J. ROBLEDO‐ARNUNCIO S. C. GONZÁLEZ‐MARTÍNEZ P. E. SMOUSE R. ALÍA 《Molecular ecology》2010,19(7):1396-1409
Quaternary climatic fluctuations have left contrasting historical footprints on the neutral genetic diversity patterns of existing populations of different tree species. We should expect the demography, and consequently the neutral genetic structure, of taxa less tolerant to particular climatic extremes to be more sensitive to long‐term climate fluctuations. We explore this hypothesis here by sampling all six pine species found in the Iberian Peninsula (2464 individuals, 105 populations), using a common set of chloroplast microsatellite markers, and by looking at the association between neutral genetic diversity and species‐specific climatic requirements. We found large variation in neutral genetic diversity and structure among Iberian pines, with cold‐enduring mountain species (Pinus uncinata, P. sylvestris and P. nigra) showing substantially greater diversity than thermophilous taxa (P. pinea and P. halepensis). Within species, we observed a significant positive correlation between population genetic diversity and summer precipitation for some of the mountain pines. The observed pattern is consistent with the hypotheses that: (i) more thermophilous species have been subjected to stronger demographic fluctuations in the past, as a consequence of their maladaptation to recurrent glacial cold stages; and (ii) altitudinal migrations have allowed the maintenance of large effective population sizes and genetic variation in cold‐tolerant species, especially in more humid regions. In the light of these results and hypotheses, we discuss some potential genetic consequences of impending climate change. 相似文献
159.
QIANQIAN ZHANG XINPENG FAN JOHN C. CLAMP KHALED A. S. AL‐RASHEID WEIBO SONG 《The Journal of eukaryotic microbiology》2010,57(6):483-493
ABSTRACT. The marine scuticociliate Paratetrahymena parawassi n. sp. is described on the basis of morphology, especially infraciliature, and the sequence of its small subunit (SSU) rRNA gene to become the second known member of its genus. Paratetrahymena and other ciliates in the order Loxocephalida possess a mixture of morphological and morphogenetic features characteristic of the subclasses Hymenostomatia and Scuticociliatia. Accordingly, we used SSU rRNA sequences to analyze the phylogeny of Paratetrahymena and three other loxocephalid genera. Paratetrahymena and Cardiostomatella vermiformis formed a moderately well‐supported clade that diverged at a deep level from all other scuticociliates, supporting separation of loxocephalids from other scuticociliates as a suprafamilial taxon. Sathrophilus holtae was a sister taxon to Paratetrahymena and Cardiostomatella in a poorly supported, unresolved relationship; nevertheless, association of all three genera into a single clade was supported by an approximately unbiased (AU) test. Any association of these genera singly or as a group with the Hymenostomatia was rejected decisively by AU tests and by a complete absence in the loxocephalids of the unique nucleotide identities that distinguish hymenostomes. Therefore, the morphological and morphogenetic similarities of loxocephalids to hymenostomes may be plesiomorphies, and the conflicting mix of scuticociliate and hymenostome characteristics seen in loxocephalids may result from differing rates of character evolution. Dexiotrichides pangi and Urocentrum, which is currently classified as a peniculid, formed a small clade that associated with hymenostomes and peritrichs. Monophyly of the Loxocephalida with Dexiotrichides and/or Urocentrum included was not rejected by AU; however, inclusion of Urocentrum in the Peniculia was rejected by AU tests. A hypothesis is offered to explain the lack of resolution of loxocephalid ciliates and Urocentrum in phylogenetic trees, namely that their phylogenetic positions are influenced by a combination of heterogeneous data and long‐branch attraction caused by poor representation of taxa in analyses. The well‐known genus Cyclidium, a member of the order Pleuronematida, was revealed to be polyphyletic as a byproduct of our analyses of loxocephalids. In particular, Cyclidium porcatum appears to fall outside the clade containing typical members of the subclass Scuticociliatia and thus invites investigation as a possible member of the order Loxocephalida. 相似文献
160.