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101.
Familial dementia caused by polymerization of mutant neuroserpin. 总被引:13,自引:0,他引:13
R L Davis A E Shrimpton P D Holohan C Bradshaw D Feiglin G H Collins P Sonderegger J Kinter L M Becker F Lacbawan D Krasnewich M Muenke D A Lawrence M S Yerby C M Shaw B Gooptu P R Elliott J T Finch R W Carrell D A Lomas 《Nature》1999,401(6751):376-379
Aberrant protein processing with tissue deposition is associated with many common neurodegenerative disorders; however, the complex interplay of genetic and environmental factors has made it difficult to decipher the sequence of events linking protein aggregation with clinical disease. Substantial progress has been made toward understanding the pathophysiology of prototypical conformational diseases and protein polymerization in the superfamily of serine proteinase inhibitors (serpins). Here we describe a new disease, familial encephalopathy with neuroserpin inclusion bodies, characterized clinically as an autosomal dominantly inherited dementia, histologically by unique neuronal inclusion bodies and biochemically by polymers of the neuron-specific serpin, neuroserpin. We report the cosegregation of point mutations in the neuroserpin gene (PI12) with the disease in two families. The significance of one mutation, S49P, is evident from its homology to a previously described serpin mutations, whereas that of the other, S52R, is predicted by modelling of the serpin template. Our findings provide a molecular mechanism for a familial dementia and imply that inhibitors of protein polymerization may be effective therapies for this disorder and perhaps for other more common neurodegenerative diseases. 相似文献
102.
103.
K. L. Becker O. L. Silva J. Cyrus R. H. Snider Jr. C. F. Moore 《Cellular and molecular life sciences : CMLS》1980,36(11):1330-1331
Summary Gastrin has been suggested as a natural secretogogue of the hormone calcitonin. We have found hypercalcitonemia in 55% of patients with pernicious anemia, and the gastrin levels, although usually increased, did not correlate. 相似文献
104.
105.
106.
H. W. Becker 《Cellular and molecular life sciences : CMLS》1965,21(12):719-719
Zusammenfassung Im zweiten Abdominalganglion der Indischen Stabheuschrecke (Carausius morosus Br.) wurden 600 ± 50 Neurone, 1000 ± 100 Gliazellen und 500 ± 30 Perineuriumzellen, zusammen etwa 2100 Zellen gezählt. Die Volumina des Ganglions, des Neuropilems und des Zellcortex betrugen etwa: 140 · 10–4 mm3, 75 · 10–4 mm3 und 65 · 10–4 mm3. 相似文献
107.
Gemoll T Roblick UJ Szymczak S Braunschweig T Becker S Igl BW Bruch HP Ziegler A Hellman U Difilippantonio MJ Ried T Jörnvall H Auer G Habermann JK 《Cellular and molecular life sciences : CMLS》2011,68(19):3261-3274
DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n?=?19), diploid (n?=?31), and aneuploid (n?=?47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers. 相似文献
108.
109.
Becker T Franckenberg S Wickles S Shoemaker CJ Anger AM Armache JP Sieber H Ungewickell C Berninghausen O Daberkow I Karcher A Thomm M Hopfner KP Green R Beckmann R 《Nature》2012,482(7386):501-506
Ribosome-driven protein biosynthesis is comprised of four phases: initiation, elongation, termination and recycling. In bacteria, ribosome recycling requires ribosome recycling factor and elongation factor G, and several structures of bacterial recycling complexes have been determined. In the eukaryotic and archaeal kingdoms, however, recycling involves the ABC-type ATPase ABCE1 and little is known about its structural basis. Here we present cryo-electron microscopy reconstructions of eukaryotic and archaeal ribosome recycling complexes containing ABCE1 and the termination factor paralogue Pelota. These structures reveal the overall binding mode of ABCE1 to be similar to canonical translation factors. Moreover, the iron-sulphur cluster domain of ABCE1 interacts with and stabilizes Pelota in a conformation that reaches towards the peptidyl transferase centre, thus explaining how ABCE1 may stimulate peptide-release activity of canonical termination factors. Using the mechanochemical properties of ABCE1, a conserved mechanism in archaea and eukaryotes is suggested that couples translation termination to recycling, and eventually to re-initiation. 相似文献
110.
Andrés E Askebjer P Bai X Barouch G Barwick SW Bay RC Becker KH Bergström L Bertrand D Bierenbaum D Biron A Booth J Botner O Bouchta A Boyce MM Carius S Chen A Chirkin D Conrad J Cooley J Costa CG Cowen DF Dailing J Dalberg E DeYoung T Desiati P Dewulf JP Doksus P Edsjö J Ekström P Erlandsson B Feser T Gaug M Goldschmidt A Goobar A Gray L Haase H Hallgren A Halzen F Hanson K Hardtke R He YD Hellwig M Heukenkamp H Hill GC Hulth PO Hundertmark S Jacobsen J Kandhadai V Karle A Kim J Koci B Köpke L 《Nature》2001,410(6827):441-443
Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water or ice. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations. 相似文献