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1.
Danilo Capecchi Giuseppe Ruta Patrizia Trovalusci 《Archive for History of Exact Sciences》2010,64(5):525-559
In the first decades of the nineteenth century the French mechanicians—Cauchy and Poisson amongst them—developed a theory
of linear elasticity according to which matter is composed of material points. They believed that these points interact by
means of opposite central forces, whose magnitude depends on the length of the segment joining the particles. This theory
suggested that homogeneous isotropic materials were characterized by a unique elastic constant. Later experiments, however,
showed that two elastic constants were necessary. These results undermined the corpuscular model of matter as well as the
interpretation of elasticity in terms of central intermolecular actions. The continuous theory of Green, based on the postulate
that a potential function exists, gained fresh consensus in light of these experiments. These opposite views continued throughout
the nineteenth century until Woldemar Voigt proposed a molecular model confirmed by experiments. This article presents the
theories of each of these scientists and describes the contrasting views of nineteenth-century mechanicians. 相似文献
2.
The knockout mouse project 总被引:1,自引:0,他引:1
Austin CP Battey JF Bradley A Bucan M Capecchi M Collins FS Dove WF Duyk G Dymecki S Eppig JT Grieder FB Heintz N Hicks G Insel TR Joyner A Koller BH Lloyd KC Magnuson T Moore MW Nagy A Pollock JD Roses AD Sands AT Seed B Skarnes WC Snoddy J Soriano P Stewart DJ Stewart F Stillman B Varmus H Varticovski L Verma IM Vogt TF von Melchner H Witkowski J Woychik RP Wurst W Yancopoulos GD Young SG Zambrowicz B 《Nature genetics》2004,36(9):921-924
Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. 相似文献
3.
The expression pattern and activity of fibroblast growth factor-8 (FGF8) in experimental assays indicate that it has important roles in limb development, but early embryonic lethality resulting from mutation of Fgf8 in the germ line of mice has prevented direct assessment of these roles. Here we report that conditional disruption of Fgf8 in the forelimb of developing mice bypasses embryonic lethality and reveals a requirement for Fgf8 in the formation of the stylopod, anterior zeugopod and autopod. Lack of Fgf8 in the apical ectodermal ridge (AER) alters expression of other Fgf genes, Shh and Bmp2. 相似文献
4.
Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene Hox-1.6. 总被引:19,自引:0,他引:19
Gene targeting in mouse embryo-derived stem cells has been used to generate mice with a disruption in the homeobox gene Hox-1.6. Mice heterozygous at the Hox-1.6 locus appear normal, whereas Hox-1.6-/Hox-1.6- mice die at or shortly after birth. These homozygotes exhibit profound defects in the formation of the external, middle and inner ears as well as in specific hindbrain nuclei, and in cranial nerves and ganglia. The affected tissues lie within a narrow region along the anteroposterior axis of the mouse but are of diverse embryonic origin. The set of defects associated with the disruption of Hox-1.6 is distinct from and nonoverlapping with that of the closely linked Hox-1.5 gene. But both mutations cause loss, rather than homeotic transformation, of tissues and structures. 相似文献
5.
Introduction of homologous DNA sequences into mammalian cells induces mutations in the cognate gene 总被引:44,自引:0,他引:44
Injection of homologous DNA sequences into nuclei of cultured mammalian cells induces mutations in the cognate chromosomal gene. It appears that these mutations result from incorrect repair of a heteroduplex formed between the introduced and the chromosomal sequence. This phenomenon is termed 'heteroduplex induced mutagenesis'. The high frequency of these events suggests that this method may prove useful for introducing mutations into specific mammalian genes. 相似文献
6.
Biological diversity is driven mainly by gene duplication followed by mutation and selection. This divergence in either regulatory or protein-coding sequences can result in quite different biological functions for even closely related genes. This concept is exemplified by the mammalian Hox gene complex, a group of 39 genes which are located on 4 linkage groups, dispersed on 4 chromosomes. The evolution of this complex began with amplification in cis of a primordial Hox gene to produce 13 members, followed by duplications in trans of much of the entire unit. As a consequence, Hox genes that occupy the same relative position along the 5' to 3' chromosomal coordinate (trans-paralogous genes) share more similarity in sequence and expression pattern than do adjacent Hox genes on the same chromosome. Studies in mice indicate that although individual family members may have unique biological roles, they also share overlapping functions with their paralogues. Here we show that the proteins encoded by the paralogous genes, Hoxa3 and Hoxd3, can carry out identical biological functions, and that the different roles attributed to these genes are the result of quantitative modulations in gene expression. 相似文献
7.
Release factors mediating termination of complete proteins 总被引:7,自引:0,他引:7
8.
低碳锰钢中周期性带状组织 总被引:6,自引:0,他引:6
用扫描电镜和电子探针研究了低碳锰钢中的周期性带状组织,结果表明,在全部研究用钢中,钢锭经热轧后均出现这种组织,其严重程度随钢的成分而异,并随坯带加工顺序而增加,带状组织与锰的显微偏析等因素有关,适当的调整碳锰以及形成模跨铁素体带的转变产物可降低带状组织的严重程度。 相似文献
9.
Gene targeting in mouse embryo-derived stem cells has been used to disrupt the homeobox gene hox-1.5. Mice heterozygous at the hox-1.5 locus appear normal, whereas hox-1.5-/hox-1.5- mice die at or shortly after birth. These homozygotes are athymic, aparathyroid, have reduced thyroid and submaxillary tissue and exhibit a wide range of throat abnormalities. In addition, they often feature defects of the heart and arteries as well as craniofacial abnormalities. These deficiencies are remarkably similar to the pathology of the human congenital disorder DiGeorge's syndrome. 相似文献
10.
Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes 总被引:223,自引:0,他引:223
Gene targeting--homologous recombination of DNA sequences residing in the chromosome with newly introduced DNA sequences--in mouse embryo-derived stem cells promises to provide a means to generate mice of any desired genotype. We describe a positive nd negative selection procedure that enriches 2,000-fold for those cells that contain a targeted mutation. The procedure was applied to the isolation of hprt- and int-2- mutants, but it should be applicable to any gene. 相似文献