全文获取类型
收费全文 | 572篇 |
免费 | 36篇 |
国内免费 | 2篇 |
出版年
2021年 | 7篇 |
2020年 | 5篇 |
2019年 | 7篇 |
2018年 | 7篇 |
2017年 | 11篇 |
2016年 | 5篇 |
2015年 | 13篇 |
2014年 | 20篇 |
2013年 | 33篇 |
2012年 | 22篇 |
2011年 | 29篇 |
2010年 | 22篇 |
2009年 | 27篇 |
2008年 | 28篇 |
2007年 | 19篇 |
2006年 | 16篇 |
2005年 | 12篇 |
2004年 | 15篇 |
2003年 | 14篇 |
2002年 | 10篇 |
2001年 | 23篇 |
2000年 | 14篇 |
1999年 | 11篇 |
1998年 | 11篇 |
1997年 | 9篇 |
1996年 | 8篇 |
1995年 | 5篇 |
1994年 | 7篇 |
1993年 | 10篇 |
1992年 | 11篇 |
1991年 | 8篇 |
1990年 | 9篇 |
1989年 | 12篇 |
1988年 | 14篇 |
1987年 | 9篇 |
1986年 | 10篇 |
1985年 | 15篇 |
1984年 | 7篇 |
1981年 | 5篇 |
1979年 | 9篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1975年 | 4篇 |
1974年 | 8篇 |
1973年 | 4篇 |
1970年 | 4篇 |
1968年 | 3篇 |
1967年 | 3篇 |
1966年 | 3篇 |
1965年 | 4篇 |
排序方式: 共有610条查询结果,搜索用时 31 毫秒
41.
Evolutionary distances for protein-coding sequences: modeling site- specific residue frequencies 总被引:13,自引:8,他引:5
Estimation of evolutionary distances from coding sequences must take into
account protein-level selection to avoid relative underestimation of longer
evolutionary distances. Current modeling of selection via site-to-site rate
heterogeneity generally neglects another aspect of selection, namely
position-specific amino acid frequencies. These frequencies determine the
maximum dissimilarity expected for highly diverged but functionally and
structurally conserved sequences, and hence are crucial for estimating long
distances. We introduce a codon- level model of coding sequence evolution
in which position-specific amino acid frequencies are free parameters. In
our implementation, these are estimated from an alignment using methods
described previously. We use simulations to demonstrate the importance and
feasibility of modeling such behavior; our model produces linear distance
estimates over a wide range of distances, while several alternative models
underestimate long distances relative to short distances. Site-to-site
differences in rates, as well as synonymous/nonsynonymous and
first/second/third-codon-position differences, arise as a natural
consequence of the site-to-site differences in amino acid frequencies.
相似文献
42.
High-level expression of the Endo-beta-N-acetylglucosaminidase F2 gene in E.coli: one step purification to homogeneity 总被引:1,自引:0,他引:1
The Endo F2gene was overexpressed in E.coli as a fusion protein joined to
the maltose-binding protein. MBP-Endo F2was found in a highly enriched
state as insoluble, inactive inclusion bodies. Extraction of the inclusion
bodies with 20% acetic acid followed by exhaustive dialysis rendered the
fusion protein active and soluble. MBP-Endo F2was digested with Factor
Xaand purified on Q-Sepharose. The enzyme was homogeneous by SDS-PAGE, and
appeared as a single symmetrical peak on HPLC. Analysis of the
amino-terminus demonstrated conclusively that recombinant Endo F2was
homogeneous and identical to the native enzyme.
相似文献
43.
44.
Autism spectrum disorders (ASDs) are highly heritable and characterised by deficits in social interaction and communication, as well as restricted and repetitive behaviours. Although a number of highly penetrant ASD gene variants have been identified, there is growing evidence to support a causal role for combinatorial effects arising from the contributions of multiple loci. By examining synaptic and circadian neurological phenotypes resulting from the dosage variants of unique human:fly orthologues in Drosophila, we observe numerous synergistic interactions between pairs of informatically-identified candidate genes whose orthologues are jointly affected by large de novo copy number variants (CNVs). These CNVs were found in the genomes of individuals with autism, including a patient carrying a 22q11.2 deletion. We first demonstrate that dosage alterations of the unique Drosophila orthologues of candidate genes from de novo CNVs that harbour only a single candidate gene display neurological defects similar to those previously reported in Drosophila models of ASD-associated variants. We then considered pairwise dosage changes within the set of orthologues of candidate genes that were affected by the same single human de novo CNV. For three of four CNVs with complete orthologous relationships, we observed significant synergistic effects following the simultaneous dosage change of gene pairs drawn from a single CNV. The phenotypic variation observed at the Drosophila synapse that results from these interacting genetic variants supports a concordant phenotypic outcome across all interacting gene pairs following the direction of human gene copy number change. We observe both specificity and transitivity between interactors, both within and between CNV candidate gene sets, supporting shared and distinct genetic aetiologies. We then show that different interactions affect divergent synaptic processes, demonstrating distinct molecular aetiologies. Our study illustrates mechanisms through which synergistic effects resulting from large structural variation can contribute to human disease. 相似文献
45.
46.
BUALUANG FAIYUE MOHAMMED J. AL‐AZZAWI TIMOTHY J. FLOWERS 《Plant, cell & environment》2010,33(5):702-716
Although an apoplastic pathway (the so‐called bypass flow) is implicated in the uptake of Na+ by rice growing in saline conditions, the point of entry of this flow into roots remains to be elucidated. We investigated the role of lateral roots in bypass flow using the tracer trisodium‐8‐hydroxy‐1,3,6‐pyrenetrisulphonic acid (PTS) and the rice cv. IR36. PTS was identified in the vascular tissue of lateral roots using both epifluorescence microscopy and confocal laser scanning microscopy. Cryo‐scanning electron microscopy and epifluorescence microscopy of sections stained with berberine‐aniline blue revealed that the exodermis is absent in the lateral roots. We conclude that PTS can move freely through the cortical layers of lateral roots, enter the stele and be transported to the shoot via the transpiration stream. 相似文献
47.
Rajagopal Subramanyam Craig Jolley Balakumar Thangaraj Sreedhar Nellaepalli Andrew N. Webber Petra Fromme 《Planta》2010,231(4):913-922
The effect of high salt concentration (100 mM NaCl) on the organization of photosystem I-light harvesting complex I supercomplexes
(PSI-LHCI) of Chlamydomonas reinhardtii was studied. The electron transfer activity was reduced by 39% in isolated PSI-LHCI supercomplexes. The visible circular
dichroism (CD) spectra associated with strongly coupled chlorophyll (Chl) dimers were reduced in intensity, indicating that
pigment–pigment interactions were disrupted. This data is consistent with results from fluorescence streak camera spectroscopy,
which suggest that red-shifted pigments in the PSI-LHCI antenna had been lost. Denaturing gel electrophoresis and immunoblot
analysis reveals that levels of the PSI reaction center proteins PsaD, PsaE and PsaF were reduced due to salt stress. PsaE
is almost completely absent under high salt conditions. It is known that the membrane-extrinsic subunits PsaD and E form the
ferredoxin-docking site. Our results indicate that the PSI-LHCI supercomplex is damaged by reactive oxygen species at high
salt concentration, with particular impact on the ferredoxin-docking site and the PSI-LHCI interface. 相似文献
48.
Jayne Y. Hehir-Kwa Nienke Wieskamp Caleb Webber Rolph Pfundt Han G. Brunner Christian Gilissen Bert B. A. de Vries Chris P. Ponting Joris A. Veltman 《PLoS computational biology》2010,6(4)
Copy number variants (CNVs) have recently been recognized as a common form of genomic variation in humans. Hundreds of CNVs can be detected in any individual genome using genomic microarrays or whole genome sequencing technology, but their phenotypic consequences are still poorly understood. Rare CNVs have been reported as a frequent cause of neurological disorders such as mental retardation (MR), schizophrenia and autism, prompting widespread implementation of CNV screening in diagnostics. In previous studies we have shown that, in contrast to benign CNVs, MR-associated CNVs are significantly enriched in genes whose mouse orthologues, when disrupted, result in a nervous system phenotype. In this study we developed and validated a novel computational method for differentiating between benign and MR-associated CNVs using structural and functional genomic features to annotate each CNV. In total 13 genomic features were included in the final version of a Naïve Bayesian Tree classifier, with LINE density and mouse knock-out phenotypes contributing most to the classifier''s accuracy. After demonstrating that our method (called GECCO) perfectly classifies CNVs causing known MR-associated syndromes, we show that it achieves high accuracy (94%) and negative predictive value (99%) on a blinded test set of more than 1,200 CNVs from a large cohort of individuals with MR. These results indicate that this classification method will be of value for objectively prioritizing CNVs in clinical research and diagnostics. 相似文献
49.
Constitutive polymorphic cyanogenesis in the Australian rainforest tree, Ryparosa kurrangii (Achariaceae) 总被引:1,自引:0,他引:1
Cyanogenesis, the liberation of volatile hydrogen cyanide from endogenous cyanide-containing compounds, is a proven plant defence mechanism and the particular cyanogens involved have taxonomic utility. The cyclopentenoncyanhydrin glycoside gynocardin was the only cyanogen isolated from foliar tissue of the rare Australian rainforest tree, Ryparosa kurrangii (Achariaceae). Mechanical damage simulating foliar herbivory did not induce a significant increase in the expression of cyanogenesis over a 24h period, indicating cyanogenic herbivore defence in R. kurrangii is constitutive. The cyanogenic potential of mature leaves was quantitatively polymorphic between trees in a natural population, ranging from 0.54 to 4.77 mg CN g(-1) dry wt leaf tissue. 相似文献
50.
Webber Liao Andrew Collins Matthew Hobbs Mehar S. Khatkar Junhong Luo Frank W. Nicholas 《Mammalian genome》2007,18(5):287-299
We have adapted the Location Database (LDB) map-integration strategy of Morton et al. [Ann Hum Genet 56:223–232] (1992) as
above to create an integrated map for each of several species for which fully annotated genome sequences are not yet available
(sheep, cattle, pig, wallaby), using all types of partial maps for that species, including cytogenetic, linkage, somatic-cell
hybrid, and radiation hybrid maps. An integrated map provides not only predictions of the kilobase location of every locus,
but also predicts locations (in cM) and cytogenetic band locations for every locus. In this way a comprehensive linkage map
and a comprehensive cytogenetic map are created, including all loci, irrespective of whether they have ever been linkage mapped
or physically mapped, respectively. High-resolution physical maps from annotated sequenced species have also been placed alongside
the integrated maps. This has created a powerful tool for comparative genomics. The LDB map-integration strategy has been
extended to make use of zoo-FISH comparative information. It has also been extended to enable the creation of a “virtual”
map for each species not yet sequenced by using mapping data from fully sequenced species. All of the partial maps, together
with the integrated map, for each species have been placed in a database called Comparative Location Database (CompLDB), which
is available for querying, browsing, or download in tabular form at .
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献