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11.
Faced with the common problem of dissatisfaction with the outcome of investments in information systems (IS), the IS community has long sought ways to improve information systems development (ISD). This paper reports on action research (AR) that sought to improve the effectiveness a UK university’s student record system (SRS), which had exhibited persistent problems. Critical systems thinking (CST) is seen to have value for ISD and was used to guide the AR. In the first stage of this research, the issues with the initial design of the SRS were identified to have largely resulted from insufficient elicitation of the underlying assumptions about, and perspectives on, complex organisational issues. The second stage centred on examining the situation from an “ought” perspective analysing what should be done and how, in order to develop creative solutions to the problems uncovered. The third stage involved recommending solutions to address the problems identified in order to improve the effectiveness of the SRS. Overall, the AR indicates that CST enables those involved to view the design and implementation of the SRS as a holistic system, critically reflect upon broad and complex human, technological and organisational issues from different perspectives, and thereby identify creative solutions. The main contribution of this research is in generating support for an ISD intervention guided by CST. The results of, and the understanding developed from, this intervention are likely to be relevant to the problems that frequently occur in similar situations.  相似文献   
12.
Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica are closely related Gram-negative beta-proteobacteria that colonize the respiratory tracts of mammals. B. pertussis is a strict human pathogen of recent evolutionary origin and is the primary etiologic agent of whooping cough. B. parapertussis can also cause whooping cough, and B. bronchiseptica causes chronic respiratory infections in a wide range of animals. We sequenced the genomes of B. bronchiseptica RB50 (5,338,400 bp; 5,007 predicted genes), B. parapertussis 12822 (4,773,551 bp; 4,404 genes) and B. pertussis Tohama I (4,086,186 bp; 3,816 genes). Our analysis indicates that B. parapertussis and B. pertussis are independent derivatives of B. bronchiseptica-like ancestors. During the evolution of these two host-restricted species there was large-scale gene loss and inactivation; host adaptation seems to be a consequence of loss, not gain, of function, and differences in virulence may be related to loss of regulatory or control functions.  相似文献   
13.
An SNP map of human chromosome 22   总被引:35,自引:0,他引:35  
The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.  相似文献   
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We describe a map of 1.42 million single nucleotide polymorphisms (SNPs) distributed throughout the human genome, providing an average density on available sequence of one SNP every 1.9 kilobases. These SNPs were primarily discovered by two projects: The SNP Consortium and the analysis of clone overlaps by the International Human Genome Sequencing Consortium. The map integrates all publicly available SNPs with described genes and other genomic features. We estimate that 60,000 SNPs fall within exon (coding and untranslated regions), and 85% of exons are within 5 kb of the nearest SNP. Nucleotide diversity varies greatly across the genome, in a manner broadly consistent with a standard population genetic model of human history. This high-density SNP map provides a public resource for defining haplotype variation across the genome, and should help to identify biomedically important genes for diagnosis and therapy.  相似文献   
16.
Genome sequence of Yersinia pestis, the causative agent of plague   总被引:59,自引:0,他引:59  
The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.  相似文献   
17.
D Bentley  A Toroian-Raymond 《Nature》1986,323(6090):712-715
A major question in developmental neurobiology is how developing nerve cells accurately extend processes to establish connections with their target cells. This problem involves both the nature of cues for growth cone guidance and also the question of how growth cones survey their environment for cues and respond by altering their direction of migration. The filopodia which normally extend from neuronal growth cones have been shown to affect growth cone steering in vitro and it has been proposed that they function in vivo in the detection of and response to guidance cues. This hypothesis could be tested in vivo if growth cones which normally have filopodia could be induced to migrate in their absence. The pair of Ti1 neurones are the first neurones to extend axons through the limb buds of embryonic grasshoppers. We report here an examination of the migration of Ti1 pioneer growth cones deprived of filopodia by culture in agents which disrupt actin microfilaments. Under these conditions, axons continue to extend but a large percentage of growth cones are highly disoriented. Our results indicate that Ti1 filopodia are not necessary for axonal elongation in vivo but that they are important for correctly oriented growth cone steering.  相似文献   
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Structure of insulin in 4-zinc insulin.   总被引:9,自引:0,他引:9  
G Bentley  E Dodson  G Dodson  D Hodgkin  D Mercola 《Nature》1976,261(5556):166-168
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20.
The insulin receptor is a phylogenetically ancient tyrosine kinase receptor found in organisms as primitive as cnidarians and insects. In higher organisms it is essential for glucose homeostasis, whereas the closely related insulin-like growth factor receptor (IGF-1R) is involved in normal growth and development. The insulin receptor is expressed in two isoforms, IR-A and IR-B; the former also functions as a high-affinity receptor for IGF-II and is implicated, along with IGF-1R, in malignant transformation. Here we present the crystal structure at 3.8 A resolution of the IR-A ectodomain dimer, complexed with four Fabs from the monoclonal antibodies 83-7 and 83-14 (ref. 4), grown in the presence of a fragment of an insulin mimetic peptide. The structure reveals the domain arrangement in the disulphide-linked ectodomain dimer, showing that the insulin receptor adopts a folded-over conformation that places the ligand-binding regions in juxtaposition. This arrangement is very different from previous models. It shows that the two L1 domains are on opposite sides of the dimer, too far apart to allow insulin to bind both L1 domains simultaneously as previously proposed. Instead, the structure implicates the carboxy-terminal surface of the first fibronectin type III domain as the second binding site involved in high-affinity binding.  相似文献   
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