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61.
Antibiotic resistance is ancient 总被引:7,自引:0,他引:7
D'Costa VM King CE Kalan L Morar M Sung WW Schwarz C Froese D Zazula G Calmels F Debruyne R Golding GB Poinar HN Wright GD 《Nature》2011,477(7365):457-461
The discovery of antibiotics more than 70 years ago initiated a period of drug innovation and implementation in human and animal health and agriculture. These discoveries were tempered in all cases by the emergence of resistant microbes. This history has been interpreted to mean that antibiotic resistance in pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact that collections of microbes that predate the antibiotic era are highly susceptible to antibiotics. Here we report targeted metagenomic analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments and the identification of a highly diverse collection of genes encoding resistance to β-lactam, tetracycline and glycopeptide antibiotics. Structure and function studies on the complete vancomycin resistance element VanA confirmed its similarity to modern variants. These results show conclusively that antibiotic resistance is a natural phenomenon that predates the modern selective pressure of clinical antibiotic use. 相似文献
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低频减载被认为是当电力系统发生频率严重下降事故时所能采取的最后一项补救措施.针对配电系统中的低频减载问题,文中提出了计及分布式电源和负荷静态特性的最优低频减载策略.该策略以频率及频率变化率为执行依据,并由几个基本轮和一个特殊轮组成.在基本轮中,按反馈控制律分轮次快速切除负荷,以保证频率摆脱紧急状态.而在特殊轮中,则优化... 相似文献
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Keren K Pincus Z Allen GM Barnhart EL Marriott G Mogilner A Theriot JA 《Nature》2008,453(7194):475-480
The shape of motile cells is determined by many dynamic processes spanning several orders of magnitude in space and time, from local polymerization of actin monomers at subsecond timescales to global, cell-scale geometry that may persist for hours. Understanding the mechanism of shape determination in cells has proved to be extremely challenging due to the numerous components involved and the complexity of their interactions. Here we harness the natural phenotypic variability in a large population of motile epithelial keratocytes from fish (Hypsophrys nicaraguensis) to reveal mechanisms of shape determination. We find that the cells inhabit a low-dimensional, highly correlated spectrum of possible functional states. We further show that a model of actin network treadmilling in an inextensible membrane bag can quantitatively recapitulate this spectrum and predict both cell shape and speed. Our model provides a simple biochemical and biophysical basis for the observed morphology and behaviour of motile cells. 相似文献
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Summary ERRs Both the pineal and the SCN are elements of the vertebrate multioscillator system although the relative importance of these 2 areas probably varies between, and possibly within, the different vertebrate classes. Extraretinal photoreception is a universal feature of submammalian vertebrates, and possibly of neonatal mammals, but is absent in adult mammals. Although the pineal systems of sumammalian vertebrates are photosensitive, the pineal system has been directly implicated as an extraocular site for the perception of entraining light cycles only in amphibians. In all other submammalian vertebrates extraretinal entrainment can occur in the absence of the pineal system although it is certainly conceivable that the pineal system may act as an alternate route of photoreception. These extraretinal-extrapineal receptors are located within the brain but the exact location(s) of these receptors within the brain is unknown. The hypothalamus would be likely area for this extraretinal photoreception, however, for several reasons: 1. Neurophysiological studies have identified light sensitive neurons in the frog's hypothalamus43. 2. The avian hypothalamus is a site of photoperiodic photoreception100–103. 3. The only other light sensitive structures known in vertebrates—the pineal system and the lateral eyes—are all derived embryologically from the hypothalamus. 4. The hypothalamus appears to be the site of a circadian clock and there may be advantages in having the photoreceptors and the clock anatomically close to one another. These considerations, of course, do not exclude the possibility that other brain areas may be involved as well. The reason behind the loss of extraretinal photoreception in mammals is uncertain. The shift to exclusive retinal photoreception in mammals may have been dictated by the extensive reorganization that occurred during the evolution of the mammalian brain. Or, perhaps, the increased size of the mammalian skull and overlying tissue made direct photoreception difficult and necessitated a shift to retinal photoreception. The persistence of extraretinal photoreceptors in submammalian vertebrates, however, underscores their importance in the sensory repertoire of vertebrates. 相似文献
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对用过滤法制备的介电梯度功能材料的介电特性作了阐述,并用计算机模拟的方法研究了其对电场分布的影响,进而对其在工程实际中的应用作了讨论. 相似文献
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Levitus M Waisfisz Q Godthelp BC de Vries Y Hussain S Wiegant WW Elghalbzouri-Maghrani E Steltenpool J Rooimans MA Pals G Arwert F Mathew CG Zdzienicka MZ Hiom K De Winter JP Joenje H 《Nature genetics》2005,37(9):934-935
The protein predicted to be defective in individuals with Fanconi anemia complementation group J (FA-J), FANCJ, is a missing component in the Fanconi anemia pathway of genome maintenance. Here we identify pathogenic mutations in eight individuals with FA-J in the gene encoding the DEAH-box DNA helicase BRIP1, also called FANCJ. This finding is compelling evidence that the Fanconi anemia pathway functions through a direct physical interaction with DNA. 相似文献
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Serpin-resistant mutants of human tissue-type plasminogen activator 总被引:17,自引:0,他引:17
Tissue-type plasminogen activator (t-PA) converts the inactive zymogen, plasminogen, into the powerful protease, plasmin, which then degrades the fibrin meshwork of thrombi. To prevent systemic activation of plasminogen, plasma contains several inhibitors of t-PA, the most important of which is plasminogen activator inhibitor-1 (PAI-1), a member of the serpin superfamily. As the ability to produce serpin-resistant variants of t-PA could increase the potential of this enzyme as a thrombolytic agent, we have used the known three-dimensional structure of the complex between trypsin and bovine pancreatic trypsin inhibitor (BPTI) to model the interactions between the active site of human t-PA and PAI-1. On the basis of this model we then altered by site-directed mutagenesis those amino acids of t-PA predicted to make contact with PAI-1 but not with the substrate plasminogen. We report here that although the resulting mutants have enzymatic properties similar to those of wild-type t-PA, they display significant resistance to inhibition by PAI-1. For example, following incubation with an amount of the serpin that completely inhibits the wild-type enzyme, one variant retains 95% of its initial activity. This mutant is also resistant to inhibition by the complex mixture of serpins present in human plasma. 相似文献