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951.
952.
Susana A.L. Lobo Andrew D. Lawrence Célia V. Romão Martin J. Warren Miguel Teixeira Lígia M. Saraiva 《Biochimica et Biophysica Acta - Proteins and Proteomics》2014,1844(7):1238-1247
An alternative route for haem b biosynthesis is operative in sulfate-reducing bacteria of the Desulfovibrio genus and in methanogenic Archaea. This pathway diverges from the canonical one at the level of uroporphyrinogen III and progresses via a distinct branch, where sirohaem acts as an intermediate precursor being converted into haem b by a set of novel enzymes, named the alternative haem biosynthetic proteins (Ahb). In this work, we report the biochemical characterisation of the Desulfovibrio vulgaris AhbD enzyme that catalyses the last step of the pathway. Mass spectrometry analysis showed that AhbD promotes the cleavage of S-adenosylmethionine (SAM) and converts iron-coproporphyrin III via two oxidative decarboxylations to yield haem b, methionine and the 5′-deoxyadenosyl radical. Electron paramagnetic resonance spectroscopy studies demonstrated that AhbD contains two [4Fe–4S]2 +/1 + centres and that binding of the substrates S-adenosylmethionine and iron-coproporphyrin III induces conformational modifications in both centres. Amino acid sequence comparisons indicated that D. vulgaris AhbD belongs to the radical SAM protein superfamily, with a GGE-like motif and two cysteine-rich sequences typical for ligation of SAM molecules and iron-sulfur clusters, respectively. A structural model of D. vulgaris AhbD with putative binding pockets for the iron-sulfur centres and the substrates SAM and iron-coproporphyrin III is discussed. 相似文献
953.
Monica E. Calkins Tyler M. Moore Kathleen R. Merikangas Marcy Burstein Theodore D. Satterthwaite Warren B. Bilker Kosha Ruparel Rosetta Chiavacci Daniel H. Wolf Frank Mentch Haijun Qiu John J. Connolly Patrick A. Sleiman Hakon Hakonarson Ruben C. Gur Raquel E. Gur 《World psychiatry》2014,13(3):296-305
Little is known about the occurrence and predictors of the psychosis spectrum in large non‐clinical community samples of U.S. youths. We aimed to bridge this gap through assessment of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort, a collaborative investigation of clinical and neurobehavioral phenotypes in a prospectively accrued cohort of youths, funded by the National Institute of Mental Health. Youths (age 11‐21; N=7,054) and collateral informants (caregiver/legal guardian) were recruited through the Children's Hospital of Philadelphia and administered structured screens of psychosis spectrum symptoms, other major psychopathology domains, and substance use. Youths were also administered a computerized neurocognitive battery assessing five neurobehavioral domains. Predictors of psychosis spectrum status in physically healthy participants (N=4,848) were examined using logistic regression. Among medically healthy youths, 3.7% reported threshold psychotic symptoms (delusions and/or hallucinations). An additional 12.3% reported significant sub‐psychotic positive symptoms, with odd/unusual thoughts and auditory perceptions, followed by reality confusion, being the most discriminating and widely endorsed attenuated symptoms. A minority of youths (2.3%) endorsed subclinical negative/disorganized symptoms in the absence of positive symptoms. Caregivers reported lower symptom levels than their children. Male gender, younger age, and non‐European American ethnicity were significant predictors of spectrum status. Youths with spectrum symptoms had reduced accuracy across neurocognitive domains, reduced global functioning, and increased odds of depression, anxiety, behavioral disorders, substance use and suicidal ideation. These findings have public health relevance for prevention and early intervention. 相似文献
954.
Diane Y Kim Peter D Countway Adriane C Jones Astrid Schnetzer Warren Yamashita Christine Tung David A Caron 《The ISME journal》2014,8(3):515-530
The monthly, seasonal and interannual variability of microbial eukaryote assemblages were
examined at 5 m, the deep chlorophyll maximum, 150 m and 500 m at the
San Pedro Ocean Time-series station (eastern North Pacific). The depths spanned
transitions in temperature, light, nutrients and oxygen, and included a persistently
hypoxic environment at 500 m. Terminal restriction fragment length polymorphism was
used for the analysis of 237 samples that were collected between September 2000 and
December 2010. Spatiotemporal variability patterns of microeukaryote assemblages indicated
the presence of distinct shallow and deep communities at the SPOT station, presumably
reflecting taxa that were specifically adapted for the conditions in those environments.
Community similarity values between assemblages collected 1 month apart at each depth
ranged between ∼20% and ∼84% (averages were
∼50–59%). The assemblage at 5 m was temporally more dynamic than
deeper assemblages and also displayed substantial interannual variability during the first
∼3 years of the study. Evidence of seasonality was detected for the microbial
eukaryote assemblage at 5 m between January 2008 and December 2010 and at
150 m between September 2000 and December 2003. Seasonality was not detected for
assemblages at the deep chlorophyll a maximum, which varied in depth seasonally,
or at 500 m. Microbial eukaryote assemblages exhibited cyclical patterns in at
least 1 year at each depth, implying an annual resetting of communities. Substantial
interannual variability was detected for assemblages at all depths and represented the
largest source of temporal variability in this temperate coastal ecosystem. 相似文献
955.
Peter V Lovell Morgan Wirthlin Larry Wilhelm Patrick Minx Nathan H Lazar Lucia Carbone Wesley C Warren Claudio V Mello 《Genome biology》2014,15(12)
Background
Birds are one of the most highly successful and diverse groups of vertebrates, having evolved a number of distinct characteristics, including feathers and wings, a sturdy lightweight skeleton and unique respiratory and urinary/excretion systems. However, the genetic basis of these traits is poorly understood.Results
Using comparative genomics based on extensive searches of 60 avian genomes, we have found that birds lack approximately 274 protein coding genes that are present in the genomes of most vertebrate lineages and are for the most part organized in conserved syntenic clusters in non-avian sauropsids and in humans. These genes are located in regions associated with chromosomal rearrangements, and are largely present in crocodiles, suggesting that their loss occurred subsequent to the split of dinosaurs/birds from crocodilians. Many of these genes are associated with lethality in rodents, human genetic disorders, or biological functions targeting various tissues. Functional enrichment analysis combined with orthogroup analysis and paralog searches revealed enrichments that were shared by non-avian species, present only in birds, or shared between all species.Conclusions
Together these results provide a clearer definition of the genetic background of extant birds, extend the findings of previous studies on missing avian genes, and provide clues about molecular events that shaped avian evolution. They also have implications for fields that largely benefit from avian studies, including development, immune system, oncogenesis, and brain function and cognition. With regards to the missing genes, birds can be considered ‘natural knockouts’ that may become invaluable model organisms for several human diseases.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0565-1) contains supplementary material, which is available to authorized users. 相似文献956.
Hanneke Vlaming Tibor van Welsem Erik L de Graaf David Ontoso AF Maarten Altelaar Pedro A San-Segundo Albert JR Heck Fred van Leeuwen 《EMBO reports》2014,15(10):1077-1084
Histone H2B ubiquitination is a dynamic modification that promotes methylation of histone H3K79 and H3K4. This crosstalk is important for the DNA damage response and has been implicated in cancer. Here, we show that in engineered yeast strains, ubiquitins tethered to every nucleosome promote H3K79 and H3K4 methylation from a proximal as well as a more distal site, but only if in a correct orientation. This plasticity indicates that the exact location of the attachment site, the native ubiquitin-lysine linkage and ubiquitination cycles are not critical for trans-histone crosstalk in vivo. The flexibility in crosstalk also indicates that other ubiquitination events may promote H3 methylation. 相似文献
957.
Imran Khan Emanuel Maldonado Vítor Vasconcelos Stephen J O’Brien Warren E Johnson Agostinho Antunes 《BMC genomics》2014,15(1)
Background
Adaptation of mammals to terrestrial life was facilitated by the unique vertebrate trait of body hair, which occurs in a range of morphological patterns. Keratin associated proteins (KRTAPs), the major structural hair shaft proteins, are largely responsible for hair variation.Results
We exhaustively characterized the KRTAP gene family in 22 mammalian genomes, confirming the existence of 30 KRTAP subfamilies evolving at different rates with varying degrees of diversification and homogenization. Within the two major classes of KRTAPs, the high cysteine (HS) subfamily experienced strong concerted evolution, high rates of gene conversion/recombination and high GC content. In contrast, high glycine-tyrosine (HGT) KRTAPs showed evidence of positive selection and low rates of gene conversion/recombination. Species with more hair and of higher complexity tended to have more KRATP genes (gene expansion). The sloth, with long and coarse hair, had the most KRTAP genes (175 with 141 being intact). By contrast, the “hairless” dolphin had 35 KRTAPs and the highest pseudogenization rate (74% relative to the 19% mammalian average). Unique hair-related phenotypes, such as scales (armadillo) and spines (hedgehog), were correlated with changes in KRTAPs. Gene expression variation probably also influences hair diversification patterns, for example human have an identical KRTAP repertoire as apes, but much less hair.Conclusions
We hypothesize that differences in KRTAP gene repertoire and gene expression, together with distinct rates of gene conversion/recombination, pseudogenization and positive selection, are likely responsible for micro and macro-phenotypic hair diversification among mammals in response to adaptations to ecological pressures.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-779) contains supplementary material, which is available to authorized users. 相似文献958.
Kristina Warton Vita Lin Tina Navin Nicola J Armstrong Warren Kaplan Kevin Ying Brian Gloss Helena Mangs Shalima S Nair Neville F Hacker Robert L Sutherland Susan J Clark Goli Samimi 《BMC genomics》2014,15(1)
Background
Free circulating DNA (fcDNA) has many potential clinical applications, due to the non-invasive way in which it is collected. However, because of the low concentration of fcDNA in blood, genome-wide analysis carries many technical challenges that must be overcome before fcDNA studies can reach their full potential. There are currently no definitive standards for fcDNA collection, processing and whole-genome sequencing. We report novel detailed methodology for the capture of high-quality methylated fcDNA, library preparation and downstream genome-wide Next-Generation Sequencing. We also describe the effects of sample storage, processing and scaling on fcDNA recovery and quality.Results
Use of serum versus plasma, and storage of blood prior to separation resulted in genomic DNA contamination, likely due to leukocyte lysis. Methylated fcDNA fragments were isolated from 5 donors using a methyl-binding protein-based protocol and appear as a discrete band of ~180 bases. This discrete band allows minimal sample loss at the size restriction step in library preparation for Next-Generation Sequencing, allowing for high-quality sequencing from minimal amounts of fcDNA. Following sequencing, we obtained 37×106-86×106 unique mappable reads, representing more than 50% of total mappable reads. The methylation status of 9 genomic regions as determined by DNA capture and sequencing was independently validated by clonal bisulphite sequencing.Conclusions
Our optimized methods provide high-quality methylated fcDNA suitable for whole-genome sequencing, and allow good library complexity and accurate sequencing, despite using less than half of the recommended minimum input DNA.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-476) contains supplementary material, which is available to authorized users. 相似文献959.
960.
Constanza Napolitano Warren E. Johnson Jim Sanderson Stephen J. O’Brien A. Rus Hoelzel Rachel Freer Nigel Dunstone Kermit Ritland Carol E. Ritland Elie Poulin 《Conservation Genetics》2014,15(3):631-653
The guigna (Leopardus guigna) is the smallest and most-restricted New World cat species, inhabiting only around 160,000 km2 of temperate rain forests in southern South America and is currently threatened by habitat loss, fragmentation and human persecution. We investigated phylogeographic patterns of genetic diversity, demographic history and barriers to gene flow with 116 individuals sampled across the species geographic range by analyzing 1,798 base pairs of the mtDNA (496 bp HVSI region, 720 bp NADH-5 gene, 364 bp from 16S gene and 218 bp from ATP-8 gene) and 15 microsatellite loci. Mitochondrial DNA data revealed a clear phylogeographic pattern with moderate separation between northern and southern Chilean populations supporting recognized subspecific partitions based on morphology. A recent demographic expansion was inferred for the southern-most group (San Rafael Lake), presumably due to the complete coverage of this area during the last glacial period, 28000–16000 years BP. Geographical barriers such as the Andes Mountains and the Chacao Channel have partially restricted historic and more-recent gene flow and the Chiloé Island population has diverged genetically since being separated from the mainland 7000 years BP. This is the first study of the genetic structure of this threatened species throughout its whole geographic range. 相似文献