全文获取类型
收费全文 | 453篇 |
免费 | 1篇 |
国内免费 | 2篇 |
专业分类
系统科学 | 13篇 |
丛书文集 | 1篇 |
理论与方法论 | 15篇 |
现状及发展 | 80篇 |
研究方法 | 64篇 |
综合类 | 263篇 |
自然研究 | 20篇 |
出版年
2021年 | 3篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 5篇 |
2014年 | 3篇 |
2013年 | 8篇 |
2012年 | 32篇 |
2011年 | 49篇 |
2010年 | 18篇 |
2009年 | 4篇 |
2008年 | 39篇 |
2007年 | 44篇 |
2006年 | 31篇 |
2005年 | 29篇 |
2004年 | 23篇 |
2003年 | 36篇 |
2002年 | 24篇 |
2001年 | 6篇 |
2000年 | 6篇 |
1999年 | 2篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1994年 | 3篇 |
1992年 | 1篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 6篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1974年 | 6篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1968年 | 1篇 |
1967年 | 3篇 |
1966年 | 1篇 |
1962年 | 3篇 |
1961年 | 1篇 |
1960年 | 1篇 |
1955年 | 1篇 |
1948年 | 2篇 |
排序方式: 共有456条查询结果,搜索用时 15 毫秒
181.
182.
183.
Summary Less purified fractions of ribonuclease H IIa activity of calf thymus display divalent cation-dependent ribonuclease H activity and divalent cation-independent ribonuclease activity. Because the ratio of the two enzyme activities does not change during successive chromatographic procedures, we suggest that ribonuclease H IIa activity is indeed able to degrade both ssRNA and the RNA moiety of RNA·DNA-hybrids. Ribonuclease H IIa activity can therefore be differentiated from calf thymus ribonuclease H I and H IIb by its lack of ribonuclease H specificity. The native molecular mass of ribonuclease H IIa activity is between 23 and 28 kDa. Under denaturing conditions a 23 kDa-protein band copurifies with the enzyme activity suggesting that this enzyme is monomeric. 相似文献
184.
Existing statistical models for network data that are easy to estimate and fit are based on the assumption of dyad independence or conditional dyad independence if the individuals are categorized into subgroups. We discuss how such models might be overparameterized and argue that there is a need for subgrouping methods to find appropriate models. We propose clustering of dyad distributions as such a method and illustrate it by analyzing how cooperative learning methods affect friendship data for school children.Work for this report was initiated while Frank and Komaska visited the Department of Statistics at the University of California, Riverside. Partial support was provided by the Swedish Council for Research in the Humanities and Social Sciences. 相似文献
185.
A blend of small molecules regulates both mating and development in Caenorhabditis elegans 总被引:1,自引:0,他引:1
Srinivasan J Kaplan F Ajredini R Zachariah C Alborn HT Teal PE Malik RU Edison AS Sternberg PW Schroeder FC 《Nature》2008,454(7208):1115-1118
In many organisms, population-density sensing and sexual attraction rely on small-molecule-based signalling systems. In the nematode Caenorhabditis elegans, population density is monitored through specific glycosides of the dideoxysugar ascarylose (the 'ascarosides') that promote entry into an alternative larval stage, the non-feeding and highly persistent dauer stage. In addition, adult C. elegans males are attracted to hermaphrodites by a previously unidentified small-molecule signal. Here we show, by means of combinatorial activity-guided fractionation of the C. elegans metabolome, that the mating signal consists of a synergistic blend of three dauer-inducing ascarosides, which we call ascr#2, ascr#3 and ascr#4. This blend of ascarosides acts as a potent male attractant at very low concentrations, whereas at the higher concentrations required for dauer formation the compounds no longer attract males and instead deter hermaphrodites. The ascarosides ascr#2 and ascr#3 carry different, but overlapping, information, as ascr#3 is more potent as a male attractant than ascr#2, whereas ascr#2 is slightly more potent than ascr#3 in promoting dauer formation. We demonstrate that ascr#2, ascr#3 and ascr#4 are strongly synergistic, and that two types of neuron, the amphid single-ciliated sensory neuron type K (ASK) and the male-specific cephalic companion neuron (CEM), are required for male attraction by ascr#3. On the basis of these results, male attraction and dauer formation in C. elegans appear as alternative behavioural responses to a common set of signalling molecules. The ascaroside signalling system thus connects reproductive and developmental pathways and represents a unique example of structure- and concentration-dependent differential activity of signalling molecules. 相似文献
186.
Koglin A Löhr F Bernhard F Rogov VV Frueh DP Strieter ER Mofid MR Güntert P Wagner G Walsh CT Marahiel MA Dötsch V 《Nature》2008,454(7206):907-911
Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) found in bacteria, fungi and plants use two different types of thioesterases for the production of highly active biological compounds. Type I thioesterases (TEI) catalyse the release step from the assembly line of the final product where it is transported from one reaction centre to the next as a thioester linked to a 4'-phosphopantetheine (4'-PP) cofactor that is covalently attached to thiolation (T) domains. The second enzyme involved in the synthesis of these secondary metabolites, the type II thioesterase (TEII), is a crucial repair enzyme for the regeneration of functional 4'-PP cofactors of holo-T domains of NRPS and PKS systems. Mispriming of 4'-PP cofactors by acetyl- and short-chain acyl-residues interrupts the biosynthetic system. This repair reaction is very important, because roughly 80% of CoA, the precursor of the 4'-PP cofactor, is acetylated in bacteria. Here we report the three-dimensional structure of a type II thioesterase from Bacillus subtilis free and in complex with a T domain. Comparison with structures of TEI enzymes shows the basis for substrate selectivity and the different modes of interaction of TEII and TEI enzymes with T domains. Furthermore, we show that the TEII enzyme exists in several conformations of which only one is selected on interaction with its native substrate, a modified holo-T domain. 相似文献
187.
Mitra K Schaffitzel C Shaikh T Tama F Jenni S Brooks CL Ban N Frank J 《Nature》2005,438(7066):318-324
Secreted and membrane proteins are translocated across or into cell membranes through a protein-conducting channel (PCC). Here we present a cryo-electron microscopy reconstruction of the Escherichia coli PCC, SecYEG, complexed with the ribosome and a nascent chain containing a signal anchor. This reconstruction shows a messenger RNA, three transfer RNAs, the nascent chain, and detailed features of both a translocating PCC and a second, non-translocating PCC bound to mRNA hairpins. The translocating PCC forms connections with ribosomal RNA hairpins on two sides and ribosomal proteins at the back, leaving a frontal opening. Normal mode-based flexible fitting of the archaeal SecYEbeta structure into the PCC electron microscopy densities favours a front-to-front arrangement of two SecYEG complexes in the PCC, and supports channel formation by the opening of two linked SecY halves during polypeptide translocation. On the basis of our observation in the translocating PCC of two segregated pores with different degrees of access to bulk lipid, we propose a model for co-translational protein translocation. 相似文献
188.
Regional insolation forcing of late Quaternary climate change in the Southern Hemisphere 总被引:2,自引:0,他引:2
Vandergoes MJ Newnham RM Preusser F Hendy CH Lowell TV Fitzsimons SJ Hogg AG Kasper HU Schlüchter C 《Nature》2005,436(7048):242-245
In agreement with the Milankovitch orbital forcing hypothesis it is often assumed that glacial-interglacial climate transitions occurred synchronously in the Northern and Southern hemispheres of the Earth. It is difficult to test this assumption, because of the paucity of long, continuous climate records from the Southern Hemisphere that have not been dated by tuning them to the presumed Northern Hemisphere signals. Here we present an independently dated terrestrial pollen record from a peat bog on South Island, New Zealand, to investigate global and local factors in Southern Hemisphere climate changes during the last two glacial-interglacial cycles. Our record largely corroborates the Milankovitch model of orbital forcing but also exhibits some differences: in particular, an earlier onset and longer duration of the Last Glacial Maximum. Our results suggest that Southern Hemisphere insolation may have been responsible for these differences in timing. Our findings question the validity of applying orbital tuning to Southern Hemisphere records and suggest an alternative mechanism to the bipolar seesaw for generating interhemispheric asynchrony in climate change. 相似文献
189.
190.
A genome-wide scalable SNP genotyping assay using microarray technology 总被引:24,自引:0,他引:24
Oligonucleotide probe arrays have enabled massively parallel analysis of gene expression levels from a single cDNA sample. Application of microarray technology to analyzing genomic DNA has been stymied by the sequence complexity of the entire human genome. A robust, single base-resolution direct genomic assay would extend the reach of microarray technology. We developed an array-based whole-genome genotyping assay that does not require PCR and enables effectively unlimited multiplexing. The assay achieves a high signal-to-noise ratio by combining specific hybridization of picomolar concentrations of whole genome-amplified DNA to arrayed probes with allele-specific primer extension and signal amplification. As proof of principle, we genotyped several hundred previously characterized SNPs. The conversion rate, call rate and accuracy were comparable to those of high-performance PCR-based genotyping assays. 相似文献