全文获取类型
收费全文 | 229篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 7篇 |
丛书文集 | 1篇 |
教育与普及 | 1篇 |
理论与方法论 | 2篇 |
现状及发展 | 37篇 |
研究方法 | 74篇 |
综合类 | 101篇 |
自然研究 | 7篇 |
出版年
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2013年 | 5篇 |
2012年 | 19篇 |
2011年 | 32篇 |
2010年 | 13篇 |
2009年 | 1篇 |
2008年 | 20篇 |
2007年 | 16篇 |
2006年 | 22篇 |
2005年 | 15篇 |
2004年 | 19篇 |
2003年 | 15篇 |
2002年 | 12篇 |
2001年 | 1篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 4篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1967年 | 1篇 |
1958年 | 1篇 |
1957年 | 1篇 |
1956年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有230条查询结果,搜索用时 15 毫秒
51.
Liu Z Moore PH Ma H Ackerman CM Ragiba M Yu Q Pearl HM Kim MS Charlton JW Stiles JI Zee FT Paterson AH Ming R 《Nature》2004,427(6972):348-352
Many diverse systems for sex determination have evolved in plants and animals. One involves physically distinct (heteromorphic) sex chromosomes (X and Y, or Z and W) that are homozygous in one sex (usually female) and heterozygous in the other (usually male). Sex chromosome evolution is thought to involve suppression of recombination around the sex determination genes, rendering permanently heterozygous a chromosomal region that may then accumulate deleterious recessive mutations by Muller's ratchet, and fix deleterious mutations by hitchhiking as nearby favourable mutations are selected on the Y chromosome. Over time, these processes may cause the Y chromosome to degenerate and to diverge from the X chromosome over much of its length; for example, only 5% of the human Y chromosome still shows X-Y recombination. Here we show that papaya contains a primitive Y chromosome, with a male-specific region that accounts for only about 10% of the chromosome but has undergone severe recombination suppression and DNA sequence degeneration. This finding provides direct evidence for the origin of sex chromosomes from autosomes. 相似文献
52.
53.
Brigitte Cambon de Lavalette Charles Tijus Christine Leproux Olivier Bauer 《Foundations of Science》2005,10(1):25-45
Taxonomy Based modeling was applied to describe drivers’ mental models of variable message signs (VMS’s) displayed on expressways.
Progress in road telematics has made it possible to introduce variable message signs (VMS’s). Sensors embedded in the carriageway
every 500m record certain variables (speed, flow rate, etc.) that are transformed in real time into “driving times” to a given
destination if road conditions do not change.
VMS systems are auto-regulative Man-Machine (AMMI) systems which incorporate a model of the user: if the traffic flow is too
high, then drivers should choose alternative routes. In so doing, the traffic flow should decrease. The model of the user
is based on suppositions such as: people do not like to waste time, they fully understand the displayed messages, they trust
the displayed values, they know of alternative routes. However, people also have a model of the way the system functions.
And if they do not believe the contents of the message, they will not act as expected.
We collected data through interviews with drivers using the critical incidents technique (Flanagan, 1985). Results show that
the mental models that drivers have of the way the VMS system works are various but not numerous and that most of them differ
from the“ideal expert” mental model. It is clear that users don’t have an adequate model of how the VMS system works and that
VMS planners have a model of user behaviour that does not correspond to the behaviour of the drivers we interviewed. Finally,
Taxonomy Based Modeling is discussed as a tool for mental model remediation. 相似文献
54.
Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis 总被引:10,自引:0,他引:10
Parviz F Matullo C Garrison WD Savatski L Adamson JW Ning G Kaestner KH Rossi JM Zaret KS Duncan SA 《Nature genetics》2003,34(3):292-296
Although advances have been made in understanding cell differentiation, only rudimentary knowledge exists concerning how differentiated cells form tissues and organs. We studied liver organogenesis because the cell and tissue architecture of this organ is well defined. Approximately 60% of the adult liver consists of hepatocytes that are arranged as single-cell anastomosing plates extending from the portal region of the liver lobule toward the central vein. The basal surface of the hepatocytes is separated from adjacent sinusoidal endothelial cells by the space of Disse, where the exchange of substances between serum and hepatocytes takes place. The hepatocyte's apical surface forms bile canaliculi that transport bile to the hepatic ducts. Proper liver architecture is crucial for hepatic function and is commonly disrupted in disease states, including cirrhosis and hepatitis. Here we report that hepatocyte nuclear factor 4alpha (Hnf4alpha) is essential for morphological and functional differentiation of hepatocytes, accumulation of hepatic glycogen stores and generation of a hepatic epithelium. We show that Hnf4alpha is a dominant regulator of the epithelial phenotype because its ectopic expression in fibroblasts induces a mesenchymal-to-epithelial transition. Most importantly, the morphogenetic parameters controlled by Hnf4alpha in hepatocytes are essential for normal liver architecture, including the organization of the sinusoidal endothelium. 相似文献
55.
The production of defects in flow-aligning nematic liquid crystals under simple shear flow is analyzed by linear stability analysis based on Leslie-Ericksen theory. It is pointed out that the equation of motion of the nematic director under simple shear flow conforms to the driven over-damped sine-Gordon equation and has a soliton solution of amplitude π. It has also been shown that the stationary state with the director uniformly oriented at a Leslie angle is only a metastable state and that the potential, which governs the motion of the director, has infinite numbers of stable stationary states. Therefore, the defects, appearing as a stable solitary solution, can be nucleated from a uniformly aligned flow-aligning type of nematic liquid crystal by shear flow. On the other hand, the bands with long axis parallel to the vorticity axis, appearing as an unstable solution, can be observed as transient patterns at low shear rate and low shear strain value. The theoretical predictions are compared with previous experimental observations. 相似文献
56.
Park CC Ahn S Bloom JS Lin A Wang RT Wu T Sekar A Khan AH Farr CJ Lusis AJ Leahy RM Lange K Smith DJ 《Nature genetics》2008,40(4):421-429
We mapped regulatory loci for nearly all protein-coding genes in mammals using comparative genomic hybridization and expression array measurements from a panel of mouse-hamster radiation hybrid cell lines. The large number of breaks in the mouse chromosomes and the dense genotyping of the panel allowed extremely sharp mapping of loci. As the regulatory loci result from extra gene dosage, we call them copy number expression quantitative trait loci, or ceQTLs. The -2log10P support interval for the ceQTLs was <150 kb, containing an average of <2-3 genes. We identified 29,769 trans ceQTLs with -log10P > 4, including 13 hotspots each regulating >100 genes in trans. Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome. 相似文献
57.
TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis 总被引:2,自引:0,他引:2
Kabashi E Valdmanis PN Dion P Spiegelman D McConkey BJ Vande Velde C Bouchard JP Lacomblez L Pochigaeva K Salachas F Pradat PF Camu W Meininger V Dupre N Rouleau GA 《Nature genetics》2008,40(5):572-574
Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals--six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)--and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis. 相似文献
58.
Ross MT Grafham DV Coffey AJ Scherer S McLay K Muzny D Platzer M Howell GR Burrows C Bird CP Frankish A Lovell FL Howe KL Ashurst JL Fulton RS Sudbrak R Wen G Jones MC Hurles ME Andrews TD Scott CE Searle S Ramser J Whittaker A Deadman R Carter NP Hunt SE Chen R Cree A Gunaratne P Havlak P Hodgson A Metzker ML Richards S Scott G Steffen D Sodergren E Wheeler DA Worley KC Ainscough R Ambrose KD Ansari-Lari MA Aradhya S Ashwell RI Babbage AK Bagguley CL Ballabio A Banerjee R Barker GE Barlow KF 《Nature》2005,434(7031):325-337
The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. 相似文献
59.
Sweet-Cordero A Mukherjee S Subramanian A You H Roix JJ Ladd-Acosta C Mesirov J Golub TR Jacks T 《Nature genetics》2005,37(1):48-55
Using advanced gene targeting methods, generating mouse models of cancer that accurately reproduce the genetic alterations present in human tumors is now relatively straightforward. The challenge is to determine to what extent such models faithfully mimic human disease with respect to the underlying molecular mechanisms that accompany tumor progression. Here we describe a method for comparing mouse models of cancer with human tumors using gene-expression profiling. We applied this method to the analysis of a model of Kras2-mediated lung cancer and found a good relationship to human lung adenocarcinoma, thereby validating the model. Furthermore, we found that whereas a gene-expression signature of KRAS2 activation was not identifiable when analyzing human tumors with known KRAS2 mutation status alone, integrating mouse and human data uncovered a gene-expression signature of KRAS2 mutation in human lung cancer. We confirmed the importance of this signature by gene-expression analysis of short hairpin RNA-mediated inhibition of oncogenic Kras2. These experiments identified both a pattern of gene expression indicative of KRAS2 mutation and potential effectors of oncogenic KRAS2 activity in human cancer. This approach provides a strategy for using genomic analysis of animal models to probe human disease. 相似文献
60.