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1.
Single-molecule fluorescence spectroscopy has become an important research tool in the life sciences but a number of limitations hinder the widespread use as a standard technique. The limited dynamic concentration range is one of the major hurdles. Recent developments in the nanophotonic field promise to alleviate these restrictions to an extent that even low affinity biomolecular interactions can be studied. After motivating the need for nanophotonics we introduce the basic concepts of nanophotonic devices such as zero mode waveguides and nanoantennas. We highlight current applications and the future potential of nanophotonic approaches when combined with biological systems and single-molecule spectroscopy.  相似文献   
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alpha 1-Proteinase inhibitor (alpha 1-PI), a member of the serineproteinase inhibitor superfamily, has a primary role in controllingneutrophil elastase activity within the mammalian circulation. Severalstudies have indicated that the reactive center region of alpha 1-PI, theamino acid sequence of which is critical to recognition of and binding totarget proteinases, is highly divergent within and among species. Thisappears to be a consequence of accelerated rates of evolution that may havebeen driven by positive Darwinian selection. In order to examine this andother features of alpha 1-PI evolution in more detail, we have isolated andsequenced cDNAs representing alpha 1- PI mRNAs of the mouse species Mussaxicola and Mus minutoides and have compared these with a number of othermammalian alpha 1-PI mRNAs. Relative to other mammalian mRNAs, the extentof nonsynonymous substitution is generally high throughout the alpha 1-PImRNA molecule, indicating greater overall rates of amino acid substitution.Within and among mouse species, the 5'-half of the mRNA, but not the3'-half, has been homogenized by concerted evolution. Finally, the reactivecenter is under diversifying or positive Darwinian selection in muridrodents (rats, mice) and guinea pigs yet is under purifying selection inprimates and artiodactyls. The significance of these findings to alpha 1-PIfunction and the possible selective forces driving evolution of serpins ingeneral are discussed.  相似文献   
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Previous studies have shown a role for multiple drug resistance proteins in protecting the fetus from a limited number of teratogens. We have expanded the number of proteins and teratogens examined by comparing the influence of the mdr1a and mdr2 proteins on teratogen-induced orofacial clefting using their respective knockouts in crosses with the A/J, high susceptibility strain. Western blots identified the presence of mdr1a and possibly mdr2 in the placenta and fetus. The mdr1a knockout, on its unique genetic background showed lower, similar, and higher incidences of clefting compared to A/J for Dilantin, hydrocortisone (HC), and 6-aminonicotinamide (6-AN), respectively. The mdr2 knockout did not affect 6-AN clefting when compared to A/J. In reciprocal crosses, when corrected for increased spontaneous clefting, maternally inherited A/J susceptibility genes predominated over the effects of the maternal absence of mdr1a (with 6-AN). Unlike mdr1a, which had a direct effect in the fetus as shown by genotyping of affected versus unaffected fetuses, an effect of mdr2 in the fetus was not found. The mdr1a knockout was backcrossed to the A/J inbred strain for 11 generations (congenics) to eliminate genetic background effects. Reciprocal crosses showed no maternal effect from the lack of mdr1a, confirming that mdr1a expression in the fetus, rather than the placenta, protects the fetus from teratogens. Mdr2 seems not to be involved in the protection of the fetus from teratogens.  相似文献   
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Betchen  SA; Doty  RL 《Chemical senses》1998,23(4):453-457
Several fundamental questions remain enigmatic concerning human olfactorysensitivity, including (i) whether detection threshold differences existbetween the two sides of the nose (and, if so, whether such differences areinfluenced by handedness) and (ii) whether bilateral (i.e. binasal)stimulation leads to lower thresholds than unilateral stimulation (and, ifso, whether the degree of facilitation is inversely related to generalolfactory ability). In this study, and well-validated single staircaseprocedure was used to establish bilateral and unilateral detectionthresholds for the cranial nerve I stimulant phenyl ethyl alcohol in 130right- and 33 left-handed subjects. No differences in sensitivity betweenthe left and right sides of the nose were observed in either group.Bilateral thresholds were lower, on average, than unilateral thresholdswhen the latter were categorized in terms of left and right nares. However,the bilateral thresholds did not differ significantly from those of theside of the nose with the lower threshold. Overall smell ability, asmeasured by the University of Pennsylvania Smell Identification Test, didnot interact with any of the test measures. These data imply that (i) theleft and right sides of the nose do not systematically differ in detectionthreshold sensitivity for either dextrals or sinistrals and (ii) if centralintegration of left:right olfactory threshold sensitivity occurs, itseffects do not exceed the function of the better side of the nose.  相似文献   
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Academic graphs are essential for communicating complex scientific ideas and results. To ensure that these graphs truthfully reflect underlying data and relationships, visualization researchers have proposed several principles to guide the graph creation process. However, the extent of violations of these principles in academic publications is unknown. In this work, we develop a deep learning-based method to accurately measure violations of the proportional ink principle (AUC = 0.917), which states that the size of shaded areas in graphs should be consistent with their corresponding quantities. We apply our method to analyze a large sample of bar charts contained in 300K figures from open access publications. Our results estimate that 5% of bar charts contain proportional ink violations. Further analysis reveals that these graphical integrity issues are significantly more prevalent in some research fields, such as psychology and computer science, and some regions of the globe. Additionally, we find no temporal and seniority trends in violations. Finally, apart from openly releasing our large annotated dataset and method, we discuss how computational research integrity could be part of peer-review and the publication processes.  相似文献   
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The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features.  相似文献   
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The impacts of climate change on Microcystis blooms in San Francisco Estuary are uncertain because factors associated with the abundance and distribution of Microcystis blooms since their inception in 1999 are poorly understood. Discrete and continuous data collected between 2004 and 2008 were used to assess what factors controlled bloom initiation and persistence, if there was an impact of the bloom on mesozooplankton abundance and toxicity or dissolved organic carbon concentration, and how these might vary with climate change. Microcystis abundance was greater in dry years than wet years and both total microcystins concentration and the microcystins content of mesozooplankton tissue increased with abundance. The bloom began in the upstream portions of the estuary and spread farther west during dry years. Bloom initiation required water temperature above 19°C and surface irradiance in the visible range above 100 W m?2. The bloom persisted during a wide range of water quality conditions but was closely correlated with low turbidity. The intensity of Microcystis blooms will likely increase with climate change due to increased water temperature and low streamflow during droughts. Elevated water temperature earlier in the spring could also extend the duration of Microcystis blooms by up to 3 months.  相似文献   
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