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Tertius A. Hough Patrick M. Nolan Vicky Tsipouri Ayo A. Toye Ian C. Gray Michelle Goldsworthy Lee Moir Roger D. Cox Sian Clements Peter H. Glenister John Wood Rachael L. Selley Mark A. Strivens Lucie Vizor Stefan L. McCormack Josephine Peters Elizabeth M. Fisher Nigel Spurr Sohaila Rastan Joanne E. Martin Steve D.M. Brown A. Jacqueline Hunter 《Mammalian genome》2002,13(10):595-602
We used ENU mutagenesis in the mouse for the rapid generation of novel mutant phenotypes for both gene function studies and use as new animal models of human disease (Nolan et al. 2000b). One focus of the program was the development of a blood biochemistry screen. At 8-12 weeks of age, approximately 300 ml of blood was collected from F1 offspring of ENU mutagenized male mice. This yielded approximately 125 ml of plasma, used to perform a profile of 17 standard biochemical tests on an Olympus analyzer. Cohorts of F1 mice were also aged and then retested to detect late onset phenotypes. In total, 1,961 F1s were screened. Outliers were identified by running means and standard deviations. Of 70 mice showing consistent abnormalities in plasma biochemistry, 29 were entered into inheritance testing. Of these, 9 phenotypes were confirmed as inherited, 10 found not to be inherited, and 10 are still being tested. Inherited mutant phenotypes include abnormal lipid profiles (low total and HDL cholesterol, high triglycerides); abnormalities in bone and liver metabolism (low ALP, high ALP, high ALT, and AST); abnormal plasma electrolyte levels (high sodium and chloride); as well as phenotypes of interest for the study of diabetes (high glucose). The gene loci bearing the mutations are currently being mapped and further characterized. Our results have validated our biochemical screen, which is applicable to other mutagenesis projects, and we have produced a new set of mutants with defined metabolic phenotypes. 相似文献
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Ingrid Dreveny Sian E. Deeves Joel Fulton Baigong Yue Marie Messmer Amit Bhattacharya Hilary M. Collins David M. Heery 《Nucleic acids research》2014,42(2):822-835
Histone tail modifications control many nuclear processes by dictating the dynamic exchange of regulatory proteins on chromatin. Here we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A. In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated. Four crystal structures of an extended DPF alone and in complex with unmodified or acetylated forms of the H3 tail reveal the molecular basis of crosstalk between H3K4me3 and H3K14ac. We show for the first time that MOZ DPF induces α-helical conformation of H3K4-T11, revealing a unique mode of H3 recognition. The helical structure facilitates sampling of H3K4 methylation status, and proffers H3K9 and other residues for modification. Additionally, we show that a conserved double glycine hinge flanking the H3 tail helix is required for a conformational change enabling docking of H3K14ac with the DPF. In summary, our data provide the first observations of extensive helical structure in a histone tail, revealing the inherent ability of the H3 tail to adopt alternate conformations in complex with chromatin regulators. 相似文献
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High speed sCMOS‐based oblique plane microscopy applied to the study of calcium dynamics in cardiac myocytes 下载免费PDF全文
Vincent Maioli Christina Rowlands Fabiana Gordon Sian E. Harding Alexander R. Lyon Chris Dunsby 《Journal of biophotonics》2016,9(3):311-323
Oblique plane microscopy (OPM) is a form of light sheet microscopy that uses a single high numerical aperture microscope objective for both fluorescence excitation and collection. In this paper, measurements of the relative collection efficiency of OPM are presented. An OPM system incorporating two sCMOS cameras is then introduced that enables single isolated cardiac myocytes to be studied continuously for 22 seconds in two dimensions at 667 frames per second with 960 × 200 pixels and for 30 seconds with 960 × 200 × 20 voxels at 25 volumes per second. In both cases OPM is able to record in two spectral channels, enabling intracellular calcium to be studied via the probe Fluo‐4 AM simultaneously with the sarcolemma and transverse tubule network via the membrane dye Cellmask Orange. The OPM system was then applied to determine the spatial origin of spontaneous calcium waves for the first time and to measure the cell transverse tubule structure at their point of origin. Further results are presented to demonstrate that the OPM system can also be used to study calcium spark parameters depending on their relationship to the transverse tubule structure.
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Suzanne J. Ware Hubert L. Rees Sian E. Boyd Silvana N. Birchenhough 《Ecological Indicators》2009,9(4):704-718
Eleven indicators were applied to macrofaunal species abundance data obtained from four dredged material relocation sites and four aggregate extraction sites in UK waters. Indicators were subsequently scored on a scale of 0 (very poor) to 5 (excellent) according to their performance in relation to six criteria governing their utility. Number of species (S) and number of individuals (N) generally scored highest in terms of understandability, sensitivity and linkage to the human activity whilst biotic indices were assigned relatively low scores, particularly in relation to aggregate extraction activities, according to the same criteria. As the immediate consequences of dredged material relocation and aggregate extraction activities are largely physical in nature the relative insensitivity of these indices may be explained by their dependence on species responses principally to organic enrichment. Indicators that incorporated measures of relatedness of species (i.e. average taxonomic distinctness, taxonomic breadth and average phylogenetic diversity) were assigned relatively low scores due to inconsistency in identifying spatial trends, and relative insensitivity. However, such indices may have the potential advantage of illuminating the causes as well as simply the existence of change and merit further examination. The adopted approach to quantifying indicator utility is critically examined and recommendations are made for future refinements. 相似文献
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Mikko Tiusanen Tea Huotari Paul D. N. Hebert Tommi Andersson Ashley Asmus Joël Bêty Emma Davis Jennifer Gale Bess Hardwick David Hik Christian Krner Richard B. Lanctot Maarten J. J. E. Loonen Rauni Partanen Karissa Reischke Sarah T. Saalfeld Fanny Senez‐Gagnon Paul A. Smith Jn ulavík Ilkka Syvnper Christine Urbanowicz Sian Williams Paul Woodard Yulia Zaika Tomas Roslin 《Molecular ecology》2019,28(2):318-335
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