全文获取类型
收费全文 | 177篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 2篇 |
教育与普及 | 1篇 |
理论与方法论 | 1篇 |
现状及发展 | 34篇 |
研究方法 | 39篇 |
综合类 | 98篇 |
自然研究 | 3篇 |
出版年
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 2篇 |
2014年 | 1篇 |
2013年 | 3篇 |
2012年 | 16篇 |
2011年 | 18篇 |
2010年 | 6篇 |
2009年 | 5篇 |
2008年 | 8篇 |
2007年 | 14篇 |
2006年 | 14篇 |
2005年 | 10篇 |
2004年 | 13篇 |
2003年 | 9篇 |
2002年 | 12篇 |
2001年 | 2篇 |
1999年 | 2篇 |
1994年 | 1篇 |
1991年 | 2篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 3篇 |
1969年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有178条查询结果,搜索用时 15 毫秒
91.
In nature, helical macromolecules such as collagen, chitin and cellulose are critical to the morphogenesis and functionality of various hierarchically structured materials. During tissue formation, these chiral macromolecules are secreted and undergo self-templating assembly, a process whereby multiple kinetic factors influence the assembly of the incoming building blocks to produce non-equilibrium structures. A single macromolecule can form diverse functional structures when self-templated under different conditions. Collagen type I, for instance, forms transparent corneal tissues from orthogonally aligned nematic fibres, distinctively coloured skin tissues from cholesteric phase fibre bundles, and mineralized tissues from hierarchically organized fibres. Nature's self-templated materials surpass the functional and structural complexity achievable by current top-down and bottom-up fabrication methods. However, self-templating has not been thoroughly explored for engineering synthetic materials. Here we demonstrate the biomimetic, self-templating assembly of chiral colloidal particles (M13 phage) into functional materials. A single-step process produces long-range-ordered, supramolecular films showing multiple levels of hierarchical organization and helical twist. Three distinct supramolecular structures are created by this approach: nematic orthogonal twists, cholesteric helical ribbons and smectic helicolidal nanofilaments. Both chiral liquid crystalline phase transitions and competing interfacial forces at the interface are found to be critical factors in determining the morphology of the templated structures during assembly. The resulting materials show distinctive optical and photonic properties, functioning as chiral reflector/filters and structural colour matrices. In addition, M13 phages with genetically incorporated bioactive peptide ligands direct both soft and hard tissue growth in a hierarchically organized manner. Our assembly approach provides insight into the complexities of hierarchical assembly in nature and could be expanded to other chiral molecules to engineer sophisticated functional helical-twisted structures. 相似文献
92.
Temporal dynamics and genetic control of transcription in the human prefrontal cortex 总被引:1,自引:0,他引:1
Colantuoni C Lipska BK Ye T Hyde TM Tao R Leek JT Colantuoni EA Elkahloun AG Herman MM Weinberger DR Kleinman JE 《Nature》2011,478(7370):519-523
93.
Lin YY Kiihl S Suhail Y Liu SY Chou YH Kuang Z Lu JY Khor CN Lin CL Bader JS Irizarry R Boeke JD 《Nature》2012,482(7384):251-255
First identified as histone-modifying proteins, lysine acetyltransferases (KATs) and deacetylases (KDACs) antagonize each other through modification of the side chains of lysine residues in histone proteins. Acetylation of many non-histone proteins involved in chromatin, metabolism or cytoskeleton regulation were further identified in eukaryotic organisms, but the corresponding enzymes and substrate-specific functions of the modifications are unclear. Moreover, mechanisms underlying functional specificity of individual KDACs remain enigmatic, and the substrate spectra of each KDAC lack comprehensive definition. Here we dissect the functional specificity of 12 critical human KDACs using a genome-wide synthetic lethality screen in cultured human cells. The genetic interaction profiles revealed enzyme-substrate relationships between individual KDACs and many important substrates governing a wide array of biological processes including metabolism, development and cell cycle progression. We further confirmed that acetylation and deacetylation of the catalytic subunit of the adenosine monophosphate-activated protein kinase (AMPK), a critical cellular energy-sensing protein kinase complex, is controlled by the opposing catalytic activities of HDAC1 and p300. Deacetylation of AMPK enhances physical interaction with the upstream kinase LKB1, leading to AMPK phosphorylation and activation, and resulting in lipid breakdown in human liver cells. These findings provide new insights into previously underappreciated metabolic regulatory roles of HDAC1 in coordinating nutrient availability and cellular responses upstream of AMPK, and demonstrate the importance of high-throughput genetic interaction profiling to elucidate functional specificity and critical substrates of individual human KDACs potentially valuable for therapeutic applications. 相似文献
94.
95.
Killing activity of neutrophils is mediated through activation of proteases by K+ flux 总被引:34,自引:0,他引:34
Reeves EP Lu H Jacobs HL Messina CG Bolsover S Gabella G Potma EO Warley A Roes J Segal AW 《Nature》2002,416(6878):291-297
According to the hitherto accepted view, neutrophils kill ingested microorganisms by subjecting them to high concentrations of highly toxic reactive oxygen species (ROS) and bringing about myeloperoxidase-catalysed halogenation. We show here that this simple scheme, which for many years has served as a satisfactory working hypothesis, is inadequate. We find that mice made deficient in neutrophil-granule proteases but normal in respect of superoxide production and iodinating capacity, are unable to resist staphylococcal and candidal infections. We also show that activation provokes the influx of an enormous concentration of ROS into the endocytic vacuole. The resulting accumulation of anionic charge is compensated for by a surge of K+ ions that cross the membrane in a pH-dependent manner. The consequent rise in ionic strength engenders the release of cationic granule proteins, including elastase and cathepsin G, from the anionic sulphated proteoglycan matrix. We show that it is the proteases, thus activated, that are primarily responsible for the destruction of the bacteria. 相似文献
96.
PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes 总被引:36,自引:0,他引:36
Mootha VK Lindgren CM Eriksson KF Subramanian A Sihag S Lehar J Puigserver P Carlsson E Ridderstråle M Laurila E Houstis N Daly MJ Patterson N Mesirov JP Golub TR Tamayo P Spiegelman B Lander ES Hirschhorn JN Altshuler D Groop LC 《Nature genetics》2003,34(3):267-273
DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments. 相似文献
97.
Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease 总被引:30,自引:0,他引:30
Association studies offer a potentially powerful approach to identify genetic variants that influence susceptibility to common disease, but are plagued by the impression that they are not consistently reproducible. In principle, the inconsistency may be due to false positive studies, false negative studies or true variability in association among different populations. The critical question is whether false positives overwhelmingly explain the inconsistency. We analyzed 301 published studies covering 25 different reported associations. There was a large excess of studies replicating the first positive reports, inconsistent with the hypothesis of no true positive associations (P < 10(-14)). This excess of replications could not be reasonably explained by publication bias and was concentrated among 11 of the 25 associations. For 8 of these 11 associations, pooled analysis of follow-up studies yielded statistically significant replication of the first report, with modest estimated genetic effects. Thus, a sizable fraction (but under half) of reported associations have strong evidence of replication; for these, false negative, underpowered studies probably contribute to inconsistent replication. We conclude that there are probably many common variants in the human genome with modest but real effects on common disease risk, and that studies using large samples will convincingly identify such variants. 相似文献
98.
Mycorrhizal weathering of apatite as an important calcium source in base-poor forest ecosystems 总被引:15,自引:0,他引:15
Blum JD Klaue A Nezat CA Driscoll CT Johnson CE Siccama TG Eagar C Fahey TJ Likens GE 《Nature》2002,417(6890):729-731
The depletion of calcium in forest ecosystems of the northeastern USA is thought to be a consequence of acidic deposition and to be at present restricting the recovery of forest and aquatic systems now that acidic deposition itself is declining. This depletion of calcium has been inferred from studies showing that sources of calcium in forest ecosystems namely, atmospheric deposition and mineral weathering of silicate rocks such as plagioclase, a calcium-sodium silicate do not match calcium outputs observed in forest streams. It is therefore thought that calcium is being lost from exchangeable and organically bound calcium in forest soils. Here we investigate the sources of calcium in the Hubbard Brook experimental forest, through analysis of calcium and strontium abundances and strontium isotope ratios within various soil, vegetation and hydrological pools. We show that the dissolution of apatite (calcium phosphate) represents a source of calcium that is comparable in size to known inputs from atmospheric sources and silicate weathering. Moreover, apatite-derived calcium was utilized largely by ectomycorrhizal tree species, suggesting that mycorrhizae may weather apatite and absorb the released ions directly, without the ions entering the exchangeable soil pool. Therefore, it seems that apatite weathering can compensate for some of the calcium lost from base-poor ecosystems, and should be considered when estimating soil acidification impacts and calcium cycling. 相似文献
99.
100.
R. Joel Rahn 《上海理工大学学报》1988,(1)
In previous work, the analysis of the effects of aggregating simple dynamic systems has been studied by applying methods developed for thermodynamic systems in order to take account of stochastic effects. This approach is based on the Master Equation for the probability density of the contents of a vector of system levels. The goal of these studies is to determine the dynamic characteristics of systems composed of a population of sub-systems with the same dynamic structure while accounting for novel behavior that is introduced by the process of aggregating the sub-systems into the larger system. 相似文献