全文获取类型
收费全文 | 2064篇 |
免费 | 166篇 |
专业分类
2230篇 |
出版年
2023年 | 17篇 |
2022年 | 32篇 |
2021年 | 56篇 |
2020年 | 39篇 |
2019年 | 51篇 |
2018年 | 39篇 |
2017年 | 53篇 |
2016年 | 66篇 |
2015年 | 99篇 |
2014年 | 125篇 |
2013年 | 159篇 |
2012年 | 201篇 |
2011年 | 193篇 |
2010年 | 103篇 |
2009年 | 90篇 |
2008年 | 116篇 |
2007年 | 133篇 |
2006年 | 131篇 |
2005年 | 106篇 |
2004年 | 99篇 |
2003年 | 76篇 |
2002年 | 72篇 |
2001年 | 19篇 |
2000年 | 11篇 |
1999年 | 16篇 |
1998年 | 33篇 |
1997年 | 17篇 |
1996年 | 5篇 |
1995年 | 9篇 |
1994年 | 4篇 |
1993年 | 9篇 |
1992年 | 11篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1962年 | 1篇 |
1936年 | 1篇 |
排序方式: 共有2230条查询结果,搜索用时 0 毫秒
21.
Association of dystrobrevin and regulatory subunit of protein kinase A: a new role for dystrobrevin as a scaffold for signaling proteins 总被引:1,自引:0,他引:1
Ceccarini M Grasso M Veroni C Gambara G Artegiani B Macchia G Ramoni C Torreri P Mallozzi C Petrucci TC Macioce P 《Journal of molecular biology》2007,371(5):1174-1187
The dystrophin-related and -associated protein dystrobrevin is a component of the dystrophin-associated protein complex, which directly links the cytoskeleton to the extracellular matrix. It is now thought that this complex also serves as a dynamic scaffold for signaling proteins, and dystrobrevin may play a role in this context. Since dystrobrevin involvement in signaling pathways seems to be dependent on its interaction with other proteins, we sought new insights and performed a two-hybrid screen of a mouse brain cDNA library using beta-dystrobrevin, the isoform expressed in non-muscle tissues, as bait. Among the positive clones characterized after the screen, one encodes the regulatory subunit RIalpha of the cAMP-dependent protein kinase A (PKA). We confirmed the interaction by in vitro and in vivo association assays, and mapped the binding site of beta-dystrobrevin on RIalpha to the amino-terminal region encompassing the dimerization/docking domain of PKA regulatory subunit. We also found that the domain of interaction for RIalpha is contained in the amino-terminal region of beta-dystrobrevin. We obtained evidence that beta-dystrobrevin also interacts directly with RIIbeta, and that not only beta-dystrobrevin but also alpha-dystrobrevin interacts with PKA regulatory subunits. We show that both alpha and beta-dystrobrevin are specific phosphorylation substrates for PKA and that protein phosphatase 2A (PP2A) is associated with dystrobrevins. Our results suggest a new role for dystrobrevin as a scaffold protein that may play a role in different cellular processes involving PKA signaling. 相似文献
22.
Chervaux C Grimaldi C Bolotin A Quinquis B Legrain-Raspaud S van Hylckama Vlieg JE Denariaz G Smokvina T 《Journal of bacteriology》2011,193(19):5560-5561
Bifidobacterium animalis subsp. lactis CNCM I-2494 is part of a commercialized fermented dairy product with documented health benefits revealed by multiple randomized placebo-controlled clinical trials. Here we report the complete genome sequence of this strain, which has a circular genome of 1,943,113 bp with 1,660 open reading frames and 4 ribosomal operons. 相似文献
23.
Germana Zaccagnini Anna Palmisano Tamara Canu Biagina Maimone Francesco M. Lo Russo Federico Ambrogi Carlo Gaetano Francesco De Cobelli Alessandro Del Maschio Antonio Esposito Fabio Martelli 《PloS one》2015,10(11)
Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles. 相似文献
24.
The water soluble polysaccharide produced by the green variant of tetrasporic Gigartina skottsbergii was found to be composed of D-galactose and sulfate groups in a molar ratio of 1.0:0.65. (1)H and (13)C NMR spectroscopy studies of the desulfated polysaccharide showed a major backbone structure of alternating 3-linked β-D-galactopyranosyl and 4-linked α-D-galactopyranosyl units, and minor signals ascribed to 3-O-methyl-substitution on the latter unit. Ethylation analysis of the polysaccharide indicated that the sulfate groups are mainly located at position O-2 of 4-linked α-D-galactopyranosyl residue and partially located at positions O-6 of the same unit and at position O-2 of 3-linked β-D-galactopyranosyl residue, and confirmed the presence of 3-O-methyl-galactose in minor amounts (4.4%). The sulfated d-galactan presents a similar structure to λ carrageenan but with much lower sulfation at position O-6 of the α-residue and at position O-2 of β-residue. The antioxidant capacity of the sulfated d-galactan was evaluated by the peroxyl radicals (ORAC method), hydroxyl radicals, chelating activity, and ABTS(+) assays. Kinetic results obtained in these assays were compared with those obtained for the commercial λ carrageenan. The antioxidant activity toward peroxyl radicals was higher for commercial λ carrageenan, this agrees with its higher content of sulfate group. The kinetics of the reaction of both polysaccharides with hydroxyl and ABTS(+) radicals showed a complex mechanism, but the antioxidant activity was higher for the polysaccharide from the green variant of tetrasporic Gigartina skottsbergii. 相似文献
25.
Aspergillus is a genus of mold fungi that includes more than 200 described species. Many members of the group are relevant pathogens and other species are economically important. Only one species has been analyzed for codon usage, and this was performed with a small number of genes. In this paper, we report the codon usage patterns of eight completely sequenced genomes which belong to this genus. The results suggest that selection for translational efficiency and accuracy are the major factors shaping codon usage in all of the species studied so far, and therefore they were active in the last common ancestor of the group. Composition and molecular distances analyses show that highly expressed genes evolve slower at synonymous sites. We identified a conserved core of translationally optimal codons and study the tRNA gene pool in each genome. We found that the great majority of preferred triplets match the respective cognate tRNA with more copies in the respective genome. We discuss the possible scenarios that can explain the observed differences among the species analyzed. Finally we highlight the biotechnological application of this research regarding heterologous protein expression. 相似文献
26.
Parnell JJ Park J Denef V Tsoi T Hashsham S Quensen J Tiedje JM 《Applied and environmental microbiology》2006,72(10):6607-6614
The biodegradation of polychlorinated biphenyls (PCBs) relies on the ability of aerobic microorganisms such as Burkholderia xenovorans sp. LB400 to tolerate two potential modes of toxicity presented by PCB degradation: passive toxicity, as hydrophobic PCBs potentially disrupt membrane and protein function, and degradation-dependent toxicity from intermediates of incomplete degradation. We monitored the physiological characteristics and genome-wide expression patterns of LB400 in response to the presence of Aroclor 1242 (500 ppm) under low expression of the structural biphenyl pathway (succinate and benzoate growth) and under induction by biphenyl. We found no inhibition of growth or change in fatty acid profile due to PCBs under nondegrading conditions. Moreover, we observed no differential gene expression due to PCBs themselves. However, PCBs did have a slight effect on the biosurface area of LB400 cells and caused slight membrane separation. Upon activation of the biphenyl pathway, we found growth inhibition from PCBs beginning after exponential-phase growth suggestive of the accumulation of toxic compounds. Genome-wide expression profiling revealed 47 differentially expressed genes (0.56% of all genes) under these conditions. The biphenyl and catechol pathways were induced as expected, but the quinoprotein methanol metabolic pathway and a putative chloroacetaldehyde dehydrogenase were also highly expressed. As the latter protein is essential to conversion of toxic metabolites in dichloroethane degradation, it may play a similar role in the degradation of chlorinated aliphatic compounds resulting from PCB degradation. 相似文献
27.
28.
Francesca Giampieri Md Soriful Islam Stefania Greco Massimiliano Gasparrini Tamara Y. Forbes Hernandez Giovanni Delli Carpini Stefano Raffaele Giannubilo Andrea Ciavattini Bruno Mezzetti Luca Mazzoni Franco Capocasa Mario Castellucci Maurizio Battino Pasquapina Ciarmela 《Journal of cellular physiology》2019,234(5):7622-7633
Uterine leiom yomas are benign tumors highly prevalent in reproductive women. In thecurrent study, initially, we aimed to screen five different strawberry cultivars (Alba, Clery, Portola, Tecla, and Romina) to identify efficient cultivars in terms of phytochemical characterization and biological properties by measuring phenolic and anthocyanin content as well as antioxidant capacity, and by measuring apoptotic rate and reactive oxygen species (ROS) production in uterine leiomyoma cells. Next, we focused on the most efficient ones, cultivar Alba (A) and Romina (R) as well as Romina anthocyanin (RA) fraction for their ability to regulate oxidative phosphorylation (oxygen consumption rate [OCR]) glycolysis (extracellular acidification rate [ECAR]), and also fibrosis. Leiomyoma and myometrial cells were treated with a methanolic extract of A and R (250 μg/ml) or with RA (50 μg/ml) for 48 hr to measure OCR and ECAR, as well as gene expression associated with fibrosis. In the leiomyoma cells, RA was more effective in inducing apoptosis and increasing intracellular ROS levels, followed by R and A. In myometrial cells, all strawberry treatments increased the cellular viability and decreased ROS concentrations. Leiomyoma cells showed also a significant decrease in ECAR, especially after RA treatment, while OCR was slightly increased in both myometrial and leiomyoma cells. R and RA treatment significantly decreased collagen 1A1, fibronectin, versican, and activin A messenger RNA expression in leiomyoma cells. In conclusion, this study suggests that Romina, or its anthocyanin fraction, can be developed as a therapeutic and/or preventive agent for uterine leiomyomas, confirming the healthy effects exerted by these fruits and their bioactive compounds. 相似文献
29.
In eukaryotes, GPI (glycosylphosphatidylinositol) lipid anchoring of proteins is an abundant post-translational modification. The attachment of the GPI anchor is mediated by GPI-T (GPI transamidase), a multimeric, membrane-bound enzyme located in the ER (endoplasmic reticulum). Upon modification, GPI-anchored proteins enter the secretory pathway and ultimately become tethered to the cell surface by association with the plasma membrane and, in yeast, by covalent attachment to the outer glucan layer. This work demonstrates a novel in vivo assay for GPI-T. Saccharomyces cerevisiae INV (invertase), a soluble secreted protein, was converted into a substrate for GPI-T by appending the C-terminal 21 amino acid GPI-T signal sequence from the S. cerevisiae Yapsin 2 [Mkc7p (Y21)] on to the C-terminus of INV. Using a colorimetric assay and biochemical partitioning, extracellular presentation of GPI-anchored INV was shown. Two human GPI-T signal sequences were also tested and each showed diminished extracellular INV activity, consistent with lower levels of GPI anchoring and species specificity. Human/fungal chimaeric signal sequences identified a small region of five amino acids that was predominantly responsible for this species specificity. 相似文献
30.