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71.
K S Warren 《Nature》1978,273(5664):609-612
Although the general pathology of schistosomiasis has been well understood for more than 70 years, it is only recently that it has been possible to analyse the disease at the molecular level and to understand the relationship between the number of parasites in an infected individual and the appearance of overt disease. 相似文献
72.
Chen M Kasahara N Keene DR Chan L Hoeffler WK Finlay D Barcova M Cannon PM Mazurek C Woodley DT 《Nature genetics》2002,32(4):670-675
Dystrophic epidermolysis bullosa (DEB) is a family of inherited mechano-bullous disorders caused by mutations in the human type VII collagen gene (COL7A1). Individuals with DEB lack type VII collagen and anchoring fibrils, structures that attach epidermis and dermis. The current lack of treatment for DEB is an impetus to develop gene therapy strategies that efficiently transfer and stably express genes delivered to skin cells in vivo. In this study, we delivered and expressed full-length type VII collagen using a self-inactivating minimal lentivirus-based vector. Transduction of lentiviral vectors containing the COL7A1 transgene into recessive DEB (RDEB) keratinocytes and fibroblasts (in which type VII collagen was absent) resulted in persistent synthesis and secretion of type VII collagen. Unlike RDEB parent cells, the gene-corrected cells had normal morphology, proliferative potential, matrix attachment and motility. We used these gene-corrected cells to regenerate human skin on immune-deficient mice. Human skin regenerated by gene-corrected RDEB cells had restored expression of type VII collagen and formation of anchoring fibrils at the dermal-epidermal junction in vivo. These studies demonstrate that it is possible to restore type VII collagen gene expression in RDEB skin in vivo. 相似文献
73.
Cell number and cell doubling times during the development of carrot embryoids in suspension culture
Summary A time course for the appearance of different stages in embryogenesis in carrot cell cultures is presented, together with the data on cell doubling times. Removal of auxin appears to dramatically increase the rate of cell division, particularly in early embryogenesis.Acknowledgment. GSW thanks the Science Research Council U. K. for a post graduate research studentship. 相似文献
74.
The BMP antagonist noggin regulates cranial suture fusion 总被引:11,自引:0,他引:11
During skull development, the cranial connective tissue framework undergoes intramembranous ossification to form skull bones (calvaria). As the calvarial bones advance to envelop the brain, fibrous sutures form between the calvarial plates. Expansion of the brain is coupled with calvarial growth through a series of tissue interactions within the cranial suture complex. Craniosynostosis, or premature cranial suture fusion, results in an abnormal skull shape, blindness and mental retardation. Recent studies have demonstrated that gain-of-function mutations in fibroblast growth factor receptors (fgfr) are associated with syndromic forms of craniosynostosis. Noggin, an antagonist of bone morphogenetic proteins (BMPs), is required for embryonic neural tube, somites and skeleton patterning. Here we show that noggin is expressed postnatally in the suture mesenchyme of patent, but not fusing, cranial sutures, and that noggin expression is suppressed by FGF2 and syndromic fgfr signalling. Since noggin misexpression prevents cranial suture fusion in vitro and in vivo, we suggest that syndromic fgfr-mediated craniosynostoses may be the result of inappropriate downregulation of noggin expression. 相似文献
75.
76.
McClelland M Sanderson KE Clifton SW Latreille P Porwollik S Sabo A Meyer R Bieri T Ozersky P McLellan M Harkins CR Wang C Nguyen C Berghoff A Elliott G Kohlberg S Strong C Du F Carter J Kremizki C Layman D Leonard S Sun H Fulton L Nash W Miner T Minx P Delehaunty K Fronick C Magrini V Nhan M Warren W Florea L Spieth J Wilson RK 《Nature genetics》2004,36(12):1268-1274
Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae). 相似文献
77.
From 1979 to 2001, temperatures observed globally by the mid-tropospheric channel of the satellite-borne Microwave Sounding Unit (MSU channel 2), as well as the inferred temperatures in the lower troposphere, show only small warming trends of less than 0.1 K per decade (refs 1-3). Surface temperatures based on in situ observations however, exhibit a larger warming of approximately 0.17 K per decade (refs 4, 5), and global climate models forced by combined anthropogenic and natural factors project an increase in tropospheric temperatures that is somewhat larger than the surface temperature increase. Here we show that trends in MSU channel 2 temperatures are weak because the instrument partly records stratospheric temperatures whose large cooling trend offsets the contributions of tropospheric warming. We quantify the stratospheric contribution to MSU channel 2 temperatures using MSU channel 4, which records only stratospheric temperatures. The resulting trend of reconstructed tropospheric temperatures from satellite data is physically consistent with the observed surface temperature trend. For the tropics, the tropospheric warming is approximately 1.6 times the surface warming, as expected for a moist adiabatic lapse rate. 相似文献
78.
The abundance of interstellar molecular nitrogen (N2) is of considerable importance: models of steady-state gas-phase interstellar chemistry, together with millimetre-wavelength observations of interstellar N2H+ in dense molecular clouds predict that N2 should be the most abundant nitrogen-bearing molecule in the interstellar medium. Previous attempts to detect N2 absorption in the far-ultraviolet or infrared (ice features) have hitherto been unsuccessful. Here we report the detection of interstellar N2 at far-ultraviolet wavelengths towards the moderately reddened star HD 124314 in the constellation of Centaurus. The N2 column density is larger than expected from models of diffuse clouds and significantly smaller than expected for dense molecular clouds. Moreover, the N2 abundance does not explain the observed variations in the abundance of atomic nitrogen (N I) towards high-column-density sightlines, implying that the models of nitrogen chemistry in the interstellar medium are incomplete. 相似文献
79.
Variation in DNA sequence contributes to individual differences in quantitative traits, but in humans the specific sequence variants are known for very few traits. We characterized variation in gene expression in cells from individuals belonging to three major population groups. This quantitative phenotype differs significantly between European-derived and Asian-derived populations for 1,097 of 4,197 genes tested. For the phenotypes with the strongest evidence of cis determinants, most of the variation is due to allele frequency differences at cis-linked regulators. The results show that specific genetic variation among populations contributes appreciably to differences in gene expression phenotypes. Populations differ in prevalence of many complex genetic diseases, such as diabetes and cardiovascular disease. As some of these are probably influenced by the level of gene expression, our results suggest that allele frequency differences at regulatory polymorphisms also account for some population differences in prevalence of complex diseases. 相似文献
80.
Vermulst M Bielas JH Kujoth GC Ladiges WC Rabinovitch PS Prolla TA Loeb LA 《Nature genetics》2007,39(4):540-543
Whether mitochondrial mutations cause mammalian aging, or are merely correlated with it, is an area of intense debate. Here, we use a new, highly sensitive assay to redefine the relationship between mitochondrial mutations and age. We measured the in vivo rate of change of the mitochondrial genome at a single-base pair level in mice, and we demonstrate that the mutation frequency in mouse mitochondria is more than ten times lower than previously reported. Although we observed an 11-fold increase in mitochondrial point mutations with age, we report that a mitochondrial mutator mouse was able to sustain a 500-fold higher mutation burden than normal mice, without any obvious features of rapidly accelerated aging. Thus, our results strongly indicate that mitochondrial mutations do not limit the lifespan of wild-type mice. 相似文献