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排序方式: 共有642条查询结果,搜索用时 31 毫秒
561.
Wooyoung Kim 《清华大学学报》2012,(6):645-658
The prediction of essential proteins, the minimal set required for a living cell to support cellular life, is an important task to understand the cellular processes of an organism. Fast progress in high-throughput technologies and the production of large amounts of data enable the discovery of essential proteins at the system level by analyzing Protein-Protein Interaction (PPI) networks, and replacing biological or chemical experiments. Furthermore, additional gene-level annotation information, such as Gene Ontology (GO) terms, helps to detect essential proteins with higher accuracy. Various centrality algorithms have been used to determine essential proteins in a PPI network, and, recently motif centrality GO, which is based on network motifs and GO terms, works best in detecting essential proteins in a Baker’s yeast Saccharomyces cerevisiae PPI network, compared to other centrality algorithms. However, each centrality algorithm contributes to the detection of essential proteins with different properties, which makes the integration of them a logical next step. In this paper, we construct a new feature space, named CENT-ING-GO consisting of various centrality measures and GO terms, and provide a computational approach to predict essential proteins with various machine learning techniques. The experimental results show that CENT-ING-GO feature space improves performance over the INT-GO feature space in previous work by Acencio and Lemke in 2009. We also demonstrate that pruning a PPI with informative GO terms can improve the prediction performance further. 相似文献
562.
563.
Epigenetic mechanisms in mammals 总被引:11,自引:1,他引:10
DNA and histone methylation are linked and subjected to mitotic inheritance in mammals. Yet how methylation is propagated
and maintained between successive cell divisions is not fully understood. A series of enzyme families that can add methylation
marks to cytosine nucleobases, and lysine and arginine amino acid residues has been discovered. Apart from methyltransferases,
there are also histone modification enzymes and accessory proteins, which can facilitate and/or target epigenetic marks. Several
lysine and arginine demethylases have been discovered recently, and the presence of an active DNA demethylase is speculated
in mammalian cells. A mammalian methyl DNA binding protein MBD2 and de novo DNA methyltransferase DNMT3A and DNMT3B are shown experimentally to possess DNA demethylase activity. Thus, complex mammalian
epigenetic mechanisms appear to be dynamic yet reversible along with a well-choreographed set of events that take place during
mammalian development. 相似文献
564.
Dosage compensation of the active X chromosome in mammals 总被引:20,自引:0,他引:20
Monosomy of the X chromosome owing to divergence between the sex chromosomes leads to dosage compensation mechanisms to restore balanced expression between the X and the autosomes. In Drosophila melanogaster, upregulation of the male X leads to dosage compensation. It has been hypothesized that mammals likewise upregulate their active X chromosome. Together with X inactivation, this mechanism would maintain balanced expression between the X chromosome and autosomes and between the sexes. Here, we show that doubling of the global expression level of the X chromosome leads to dosage compensation in somatic tissues from several mammalian species. X-linked genes are highly expressed in brain tissues, consistent with a role in cognitive functions. Furthermore, the X chromosome is expressed but not upregulated in spermatids and secondary oocytes, preserving balanced expression of the genome in these haploid cells. Upon fertilization, upregulation of the active X must occur to achieve the observed dosage compensation in early embryos. 相似文献
565.
Rees MI Harvey K Pearce BR Chung SK Duguid IC Thomas P Beatty S Graham GE Armstrong L Shiang R Abbott KJ Zuberi SM Stephenson JB Owen MJ Tijssen MA van den Maagdenberg AM Smart TG Supplisson S Harvey RJ 《Nature genetics》2006,38(7):801-806
Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine receptor (GlyR) alpha1 subunit (GLRA1). Genetic heterogeneity has been confirmed in rare sporadic cases, with mutations affecting other postsynaptic glycinergic proteins including the GlyR beta subunit (GLRB), gephyrin (GPHN) and RhoGEF collybistin (ARHGEF9). However, many individuals diagnosed with sporadic hyperekplexia do not carry mutations in these genes. Here we show that missense, nonsense and frameshift mutations in SLC6A5 (ref. 8), encoding the presynaptic glycine transporter 2 (GlyT2), also cause hyperekplexia. Individuals with mutations in SLC6A5 present with hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. SLC6A5 mutations result in defective subcellular GlyT2 localization, decreased glycine uptake or both, with selected mutations affecting predicted glycine and Na+ binding sites. 相似文献
566.
Lahortiga I De Keersmaecker K Van Vlierberghe P Graux C Cauwelier B Lambert F Mentens N Beverloo HB Pieters R Speleman F Odero MD Bauters M Froyen G Marynen P Vandenberghe P Wlodarska I Meijerink JP Cools J 《Nature genetics》2007,39(5):593-595
We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL. 相似文献
567.
Jeon J Park SY Chi MH Choi J Park J Rho HS Kim S Goh J Yoo S Choi J Park JY Yi M Yang S Kwon MJ Han SS Kim BR Khang CH Park B Lim SE Jung K Kong S Karunakaran M Oh HS Kim H Kim S Park J Kang S Choi WB Kang S Lee YH 《Nature genetics》2007,39(4):561-565
Rapid translation of genome sequences into meaningful biological information hinges on the integration of multiple experimental and informatics methods into a cohesive platform. Despite the explosion in the number of genome sequences available, such a platform does not exist for filamentous fungi. Here we present the development and application of a functional genomics and informatics platform for a model plant pathogenic fungus, Magnaporthe oryzae. In total, we produced 21,070 mutants through large-scale insertional mutagenesis using Agrobacterium tumefaciens-mediated transformation. We used a high-throughput phenotype screening pipeline to detect disruption of seven phenotypes encompassing the fungal life cycle and identified the mutated gene and the nature of mutation for each mutant. Comparative analysis of phenotypes and genotypes of the mutants uncovered 202 new pathogenicity loci. Our findings demonstrate the effectiveness of our platform and provide new insights on the molecular basis of fungal pathogenesis. Our approach promises comprehensive functional genomics in filamentous fungi and beyond. 相似文献
568.
Kim SH Juhnn YS Kang S Park SW Sung MW Bang YJ Song YS 《Cellular and molecular life sciences : CMLS》2006,63(7-8):930-938
The E5 oncoprotein of human papillomavirus (HPV) 16 plays an important role in early cervical carcinogenesis. Vascular endothelial
growth factor (VEGF) plays a central role in switching on the angiogenic phenotype during early cervical carcinogenesis. However,
the relationship between E5 and VEGF has not previously been examined. To clarify the regulatory role of E5 in VEGF expression,
we transferred the E5 gene into various cell types. E5 increased VEGF expression. The addition of epidermal growth factor
receptor (EGFR) inhibitor significantly suppressed VEGF expression, demonstrating that E5 stimulates VEGF expression through
the activation of EGFR. E5-mediated EGFR activation was accompanied by phosphorylation of Akt and ERK1/2, which are also involved
in VEGF expression. Furthermore, the mRNA stability of VEGF was not affected by E5, but VEGF promoter activity could be modulated
by inhibitors of the EGFR, MEK-ERK1/2 and PI3K/Akt pathways in E5-expressing cells. Collectively, these novel results suggest
that HPV 16 E5 increases VEGF expression by activating EGFR, MEK/ERK1/2 and PI3K/Akt.
Received 23 November 2005; received after revision 10 January 2006; accepted 9 February 2006 相似文献
569.
Yoshiura K Kinoshita A Ishida T Ninokata A Ishikawa T Kaname T Bannai M Tokunaga K Sonoda S Komaki R Ihara M Saenko VA Alipov GK Sekine I Komatsu K Takahashi H Nakashima M Sosonkina N Mapendano CK Ghadami M Nomura M Liang DS Miwa N Kim DK Garidkhuu A Natsume N Ohta T Tomita H Kaneko A Kikuchi M Russomando G Hirayama K Ishibashi M Takahashi A Saitou N Murray JC Saito S Nakamura Y Niikawa N 《Nature genetics》2006,38(3):324-330
Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. Here we show that a SNP, 538G --> A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type. The AA genotype corresponds to dry earwax, and GA and GG to wet type. A 27-bp deletion in ABCC11 exon 29 was also found in a few individuals of Asian ancestry. A functional assay demonstrated that cells with allele A show a lower excretory activity for cGMP than those with allele G. The allele A frequency shows a north-south and east-west downward geographical gradient; worldwide, it is highest in Chinese and Koreans, and a common dry-type haplotype is retained among various ethnic populations. These suggest that the allele A arose in northeast Asia and thereafter spread through the world. The 538G --> A SNP is the first example of DNA polymorphism determining a visible genetic trait. 相似文献
570.
Sebaihia M Wren BW Mullany P Fairweather NF Minton N Stabler R Thomson NR Roberts AP Cerdeño-Tárraga AM Wang H Holden MT Wright A Churcher C Quail MA Baker S Bason N Brooks K Chillingworth T Cronin A Davis P Dowd L Fraser A Feltwell T Hance Z Holroyd S Jagels K Moule S Mungall K Price C Rabbinowitsch E Sharp S Simmonds M Stevens K Unwin L Whithead S Dupuy B Dougan G Barrell B Parkhill J 《Nature genetics》2006,38(7):779-786
We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism. 相似文献