全文获取类型
收费全文 | 112篇 |
免费 | 2篇 |
专业分类
系统科学 | 6篇 |
理论与方法论 | 1篇 |
现状及发展 | 25篇 |
研究方法 | 34篇 |
综合类 | 46篇 |
自然研究 | 2篇 |
出版年
2021年 | 2篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 3篇 |
2013年 | 1篇 |
2012年 | 13篇 |
2011年 | 13篇 |
2010年 | 3篇 |
2009年 | 4篇 |
2008年 | 4篇 |
2007年 | 10篇 |
2006年 | 14篇 |
2005年 | 9篇 |
2004年 | 10篇 |
2003年 | 3篇 |
2002年 | 9篇 |
2001年 | 1篇 |
1997年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1971年 | 1篇 |
1961年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有114条查询结果,搜索用时 265 毫秒
101.
102.
Crossover between the human sex chromosomes during male meiosis is restricted to the terminal pseudoautosomal pairing regions. An obligatory exchange occurs in PAR1, an Xp/Yp pseudoautosomal region of 2.6 Mb, which creates a male-specific recombination 'hot domain' with a recombination rate that is about 20 times higher than the genome average. Low-resolution analysis of PAR1 suggests that crossovers are distributed fairly randomly. By contrast, linkage disequilibrium (LD) and sperm crossover analyses indicate that crossovers in autosomal regions tend to cluster into 'hot spots' of 1-2 kb that lie between islands of disequilibrium of tens to hundreds of kilobases. To determine whether at high resolution this autosomal pattern also applies to PAR1, we have examined linkage disequilibrium over an interval of 43 kb around the gene SHOX. Here we show that in northern European populations, disequilibrium decays rapidly with physical distance, which is consistent with this interval of PAR1 being recombinationally active in male meiosis. Analysis of a subregion of 9.9 kb in sperm shows, however, that crossovers are not distributed randomly, but instead cluster into an intense recombination hot spot that is very similar in morphology to autosomal hot spots. Thus, PAR1 crossover activity may be influenced by male-specific hot spots that are highly suitable for characterization by sperm DNA analysis. 相似文献
103.
Functional profiling of the Saccharomyces cerevisiae genome 总被引:1,自引:0,他引:1
Giaever G Chu AM Ni L Connelly C Riles L Véronneau S Dow S Lucau-Danila A Anderson K André B Arkin AP Astromoff A El-Bakkoury M Bangham R Benito R Brachat S Campanaro S Curtiss M Davis K Deutschbauer A Entian KD Flaherty P Foury F Garfinkel DJ Gerstein M Gotte D Güldener U Hegemann JH Hempel S Herman Z Jaramillo DF Kelly DE Kelly SL Kötter P LaBonte D Lamb DC Lan N Liang H Liao H Liu L Luo C Lussier M Mao R Menard P Ooi SL Revuelta JL Roberts CJ Rose M Ross-Macdonald P Scherens B Schimmack G 《Nature》2002,418(6896):387-391
Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics. 相似文献
104.
Amanda Pellegrino de Iraldi Angela Maria Suburo 《Cellular and molecular life sciences : CMLS》1971,27(3):289-290
Resumen Se demuestra que lap-clorofenilalanina depleciona los componentes de las vesículas sinápticas de los nervios pineales de la rata revelables por la mezcla tetróxido de osmio-yoduro de zinc pero no afecta a los revelables por tetróxido de osmio-yoduro de potasio.
This work has been supported by grants from the Consejo Nacional de Investigaciones Cientificas y Técnicas, Argentina, and National Institutes of Health, USA, No. 5 R01 NS 06953-05 NEUA. 相似文献
This work has been supported by grants from the Consejo Nacional de Investigaciones Cientificas y Técnicas, Argentina, and National Institutes of Health, USA, No. 5 R01 NS 06953-05 NEUA. 相似文献
105.
Huang AL Chen X Hoon MA Chandrashekar J Guo W Tränkner D Ryba NJ Zuker CS 《Nature》2006,442(7105):934-938
Mammals taste many compounds yet use a sensory palette consisting of only five basic taste modalities: sweet, bitter, sour, salty and umami (the taste of monosodium glutamate). Although this repertoire may seem modest, it provides animals with critical information about the nature and quality of food. Sour taste detection functions as an important sensory input to warn against the ingestion of acidic (for example, spoiled or unripe) food sources. We have used a combination of bioinformatics, genetic and functional studies to identify PKD2L1, a polycystic-kidney-disease-like ion channel, as a candidate mammalian sour taste sensor. In the tongue, PKD2L1 is expressed in a subset of taste receptor cells distinct from those responsible for sweet, bitter and umami taste. To examine the role of PKD2L1-expressing taste cells in vivo, we engineered mice with targeted genetic ablations of selected populations of taste receptor cells. Animals lacking PKD2L1-expressing cells are completely devoid of taste responses to sour stimuli. Notably, responses to all other tastants remained unaffected, proving that the segregation of taste qualities even extends to ionic stimuli. Our results now establish independent cellular substrates for four of the five basic taste modalities, and support a comprehensive labelled-line mode of taste coding at the periphery. Notably, PKD2L1 is also expressed in specific neurons surrounding the central canal of the spinal cord. Here we demonstrate that these PKD2L1-expressing neurons send projections to the central canal, and selectively trigger action potentials in response to decreases in extracellular pH. We propose that these cells correspond to the long-sought components of the cerebrospinal fluid chemosensory system. Taken together, our results suggest a common basis for acid sensing in disparate physiological settings. 相似文献
106.
A fundamental goal of sociobiology is to explain how complex social behaviour evolves, especially in social insects, the exemplars of social living. Although still the subject of much controversy, recent theoretical explanations have focused on the evolutionary origins of worker behaviour (assistance from daughters that remain in the nest and help their mother to reproduce) through expression of maternal care behaviour towards siblings. A key prediction of this evolutionary model is that traits involved in maternal care have been co-opted through heterochronous expression of maternal genes to result in sib-care, the hallmark of highly evolved social life in insects. A coupling of maternal behaviour to reproductive status evolved in solitary insects, and was a ready substrate for the evolution of worker-containing societies. Here we show that division of foraging labour among worker honey bees (Apis mellifera) is linked to the reproductive status of facultatively sterile females. We thereby identify the evolutionary origin of a widely expressed social-insect behavioural syndrome, and provide a direct demonstration of how variation in maternal reproductive traits gives rise to complex social behaviour in non-reproductive helpers. 相似文献
107.
Wang J Soisson SM Young K Shoop W Kodali S Galgoci A Painter R Parthasarathy G Tang YS Cummings R Ha S Dorso K Motyl M Jayasuriya H Ondeyka J Herath K Zhang C Hernandez L Allocco J Basilio A Tormo JR Genilloud O Vicente F Pelaez F Colwell L Lee SH Michael B Felcetto T Gill C Silver LL Hermes JD Bartizal K Barrett J Schmatz D Becker JW Cully D Singh SB 《Nature》2006,441(7091):358-361
Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity. 相似文献
108.
Dunlop MG Dobbins SE Farrington SM Jones AM Palles C Whiffin N Tenesa A Spain S Broderick P Ooi LY Domingo E Smillie C Henrion M Frampton M Martin L Grimes G Gorman M Semple C Ma YP Barclay E Prendergast J Cazier JB Olver B Penegar S Lubbe S Chander I Carvajal-Carmona LG Ballereau S Lloyd A Vijayakrishnan J Zgaga L Rudan I Theodoratou E;Colorectal Tumour Gene Identification 《Nature genetics》2012,44(7):770-776
We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC. 相似文献
109.
Kraemer N Issa L Hauck SC Mani S Ninnemann O Kaindl AM 《Cellular and molecular life sciences : CMLS》2011,68(10):1719-1736
Cyclin dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) has gained attention in the last years following
the discovery, in 2005, that recessive mutations cause primary autosomal recessive microcephaly. This disease is seen as an
isolated developmental defect of the brain, particularly of the cerebral cortex, and was thus historically also referred to
as microcephalia vera. Unraveling the pathomechanisms leading to this human disease is fascinating scientists because it can convey insight into
basic mechanisms of physiologic brain development (particularly of cortex formation). It also finds itself in the spotlight
because of its implication in trends in mammalian evolution with a massive increase in the size of the cerebral cortex in
primates. Here, we provide a timely overview of the current knowledge on the function of CDK5RAP2 and mechanisms that might
lead to disease in humans when the function of this protein is disturbed. 相似文献
110.
Loveday C Turnbull C Ramsay E Hughes D Ruark E Frankum JR Bowden G Kalmyrzaev B Warren-Perry M Snape K Adlard JW Barwell J Berg J Brady AF Brewer C Brice G Chapman C Cook J Davidson R Donaldson A Douglas F Greenhalgh L Henderson A Izatt L Kumar A Lalloo F Miedzybrodzka Z Morrison PJ Paterson J Porteous M Rogers MT Shanley S Walker L;Breast Cancer Susceptibility Collaboration 《Nature genetics》2011,43(9):879-882
Recently, RAD51C mutations were identified in families with breast and ovarian cancer. This observation prompted us to investigate the role of RAD51D in cancer susceptibility. We identified eight inactivating RAD51D mutations in unrelated individuals from 911 breast-ovarian cancer families compared with one inactivating mutation identified in 1,060 controls (P = 0.01). The association found here was principally with ovarian cancer, with three mutations identified in the 59 pedigrees with three or more individuals with ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P = 4.8 × 10(-6)). By contrast, we estimated the relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50). These data indicate that RAD51D mutation testing may have clinical utility in individuals with ovarian cancer and their families. Moreover, we show that cells deficient in RAD51D are sensitive to treatment with a PARP inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers. 相似文献