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81.
Melchers WJ Zoll J Tessari M Bakhmutov DV Gmyl AP Agol VI Heus HA 《RNA (New York, N.Y.)》2006,12(9):1671-1682
The cloverleaf structure in the 5'-untranslated region of enterovirus RNA that regulates viral RNA replication contains an evolutionarily conserved YNMG tetraloop closed by a Y-G base pair. This loop is believed to interact specifically with the viral protease 3C. To further characterize the specificity of this interaction, the tetraloop and two flanking base pairs of the poliovirus RNA were randomized, and viable viral clones were obtained using in vivo SELEX. Among many different mutants with the canonical YNMG sequences to be described elsewhere, a large-plaque-forming clone contained a deviating uGCUAg sequence. The NMR structure of a small hairpin capped with uGCUAg that we present here shows that the GCUA tetraloop adopts a novel fold, which is highly similar to that of the YNMG tetraloop with common stacking properties and hydrogen-bond interactions including an unusual syn conformation of the adenosine. Thermodynamic studies show moderate stabilities of hairpins with canonical YNMG and the novel GCUA loops, which, together with the similarity of spatial structures, illustrates that the tetraloop structure itself is crucial for the RNA-protein interaction required for the viral replication. A re-evaluation of the ribosomal secondary structure database reveals a hairpin containing a GCUA loop, which covaries with YNMG and is involved in a tertiary interaction, and in the 50S ribosomal subunit from Haloarcula marismortui the structurally comparable apex of stem-loop 35a is a recognition site for protein L2. These observations show a more general occurrence and importance of the so-far unrecognized GYYA hairpin loops. 相似文献
82.
Kopecky KJ Stepanenko V Rivkind N Voillequé P Onstad L Shakhtarin V Parshkov E Kulikov S Lushnikov E Abrosimov A Troshin V Romanova G Doroschenko V Proshin A Tsyb A Davis S 《Radiation research》2006,166(2):367-374
A population-based case-control study was conducted to estimate the radiation-related risk of thyroid cancer in persons who were exposed in childhood to (131)I from the Chernobyl accident of April 26, 1986 and to investigate the impact of uncertainties in individual dose estimates. Included were all 66 confirmed cases of primary thyroid cancer diagnosed from April 26, 1986 through September 1998 in residents of Bryansk Oblast, Russia, who were 0-19 years old at the time of the accident, along with two individually matched controls for each case. Thyroid radiation doses, estimated using a semi-empirical model based on environmental contamination data and individual characteristics, ranged from 0.00014 Gy to 2.73 Gy and had large uncertainties (median geometric standard deviation 2.2). The estimated excess relative risk (ERR) associated with radiation exposure, 48.7/Gy, was significantly greater than 0 (P = 0.00013) but had an extremely wide 95% confidence interval (4.8 to 1151/Gy). Adjusting for dose uncertainty nearly tripled the ERR to 138/Gy, although this was likely an overestimate due to limitations in the modeling of dose uncertainties. The radiation-related excess risk observed in this study is quite large, especially if the uncertainty of dose estimation is taken into account, but is not inconsistent with estimates previously reported for risk after (131)I exposure or acute irradiation from external sources. 相似文献
83.
Marina A. Katkova Georgy K. Fukin Anatoly S. Averyushkin Mikhail N. Bochkarev 《Inorganica chimica acta》2006,359(13):4289-4296
The thiolate complexes of rare earth metals Ln(SR)3 (La, HSR = 2-mercaptothiazoline (1); La, HSR = 2-mercaptobenzoxazole (2); Y, La, Sm, Eu, Tb, Gd, Er, Tm, HSR = 2-mercaptobenzothiazole (3)) were synthesized in 84-97% yield by the reactions of silylamides Ln[N(SiMe3)2]3 with respective thiols. The products were characterized by elemental analysis, IR and UV/Vis spectroscopy. The structures of 3(Eu) and 3(Er) were determined by single-crystal X-ray diffraction. All obtained compounds revealed efficient luminescence in the region 400-550 nm at 293 K assigned to the ligands emission. Besides, the luminescent spectra of thiolates 3 at 77 K displayed the phosphorescent band of the ligand at 550 nm and in the cases of 3(Eu) and 3(Tb) the sets of emissions bands characteristic for Eu3+ and Tb3+ ions. 相似文献
84.
Sorokin AA Osypov AA Dzhelyadin TR Beskaravainy PM Kamzolova SG 《Journal of bioinformatics and computational biology》2006,4(2):455-467
A comparative analysis of electrostatic patterns for 359 sigma70-specific promoters and 359 nonpromoter regions on electrostatic map of Escherichia coli genome was carried out. It was found that DNA is not a uniformly charged molecule. There are some local inhomogeneities in its electrostatic profile which correlate with promoter sequences. Electrostatic patterns of promoter DNAs can be specified due to the presence of some distinctive motifs which differ for different promoter groups and may be involved as signal elements in differential recognition of various promoters by the enzyme. Some specific electrostatic elements which are responsible for modulating promoter activities due to ADP-ribosylation of RNA polymerase alpha-subunit were found in far upstream regions of T4 phage early promoters and E. coli ribosomal promoters. 相似文献
85.
Belikova NA Vladimirov YA Osipov AN Kapralov AA Tyurin VA Potapovich MV Basova LV Peterson J Kurnikov IV Kagan VE 《Biochemistry》2006,45(15):4998-5009
During apoptosis, cytochrome c (cyt c) is released from intermembrane space of mitochondria into the cytosol where it triggers the caspase-dependent machinery. We discovered that cyt c plays another critical role in early apoptosis as a cardiolipin (CL)-specific oxygenase to produce CL hydroperoxides required for release of pro-apoptotic factors [Kagan, V. E., et al. (2005) Nat. Chem. Biol. 1, 223-232]. We quantitatively characterized the activation of peroxidase activity of cyt c by CL and hydrogen peroxide. At low ionic strength and high CL/cyt c ratios, peroxidase activity of the CL/cyt c complex was increased >50 times. This catalytic activity correlated with partial unfolding of cyt c monitored by Trp(59) fluorescence and absorbance at 695 nm (Fe-S(Met(80)) band). The peroxidase activity increase preceded the loss of protein tertiary structure. Monounsaturated tetraoleoyl-CL (TOCL) induced peroxidase activity and unfolding of cyt c more effectively than saturated tetramyristoyl-CL (TMCL). TOCL/cyt c complex was found more resistant to dissociation by high salt concentration. These findings suggest that electrostatic CL/cyt c interactions are central to the initiation of the peroxidase activity, while hydrophobic interactions are involved when cyt c's tertiary structure is lost. In the presence of CL, cyt c peroxidase activity is activated at lower H(2)O(2) concentrations than for isolated cyt c molecules. This suggests that redistribution of CL in the mitochondrial membranes combined with increased production of H(2)O(2) can switch on the peroxidase activity of cyt c and CL oxidation in mitochondria-a required step in execution of apoptosis. 相似文献
86.
Ricaut FX Kolodesnikov S Keyser-Tracqui C Alekseev AN Crubézy E Ludes B 《American journal of physical anthropology》2006,129(1):55-63
The excavation of five frozen graves at the Sytygane Syhe and Istekh-Myrane burial sites (dated at 400 years old) in central Yakutia revealed five human skeletons belonging to the Yakut population. To investigate the origin and evolution of the Yakut population as well as the kinship system between individuals buried in these two sites, DNA was extracted from bone samples and analyzed by autosomal short tandem repeats (STRs) and by sequencing hypervariable region I (HV1) of the mitochondrial DNA (mtDNA) control region. The results showed a diversity of sepulchral organizations linked probably to the social or genetic background of the subjects. Comparison of STR profiles, mitochondrial haplotypes, and haplogroups with data from Eurasian populations indicated affinities with Asian populations and suggested a relative specificity and continuity of part of the Yakut mitochondrial gene pool during the last five centuries. Moreover, our results did not support a Central Asian (with the exception of maternal lineage of West Eurasian origin) or Siberian origin of the maternal lineages of these ancient Yakut subjects, implying an ethnogenesis of the Yakut population probably more complex than previously proposed. 相似文献
87.
Conformational changes in the side chains are essential for protein-protein binding. Rotameric states and unbound- to-bound conformational changes in the surface residues were systematically studied on a representative set of protein complexes. The side-chain conformations were mapped onto dihedral angles space. The variable threshold algorithm was developed to cluster the dihedral angle distributions and to derive rotamers, defined as the most probable conformation in a cluster. Six rotamer libraries were generated: full surface, surface noninterface, and surface interface-each for bound and unbound states. The libraries were used to calculate the probabilities of the rotamer transitions upon binding. The stability of amino acids was quantified based on the transition maps. The noninterface residues' stability was higher than that of the interface. Long side chains with three or four dihedral angles were less stable than the shorter ones. The transitions between the rotamers at the interface occurred more frequently than on the noninterface surface. Most side chains changed conformation within the same rotamer or moved to an adjacent rotamer. The highest percentage of the transitions was observed primarily between the two most occupied rotamers. The probability of the transition between rotamers increased with the decrease of the rotamer stability. The analysis revealed characteristics of the surface side-chain conformational transitions that can be utilized in flexible docking protocols. 相似文献
88.
89.
Anatoly Peretyatko Samuel Teissier Sylvia De Backer Ludwig Triest 《Hydrobiologia》2012,689(1):131-146
Nutrient enrichment of aquatic ecosystems caused dramatic increase in the frequency, magnitude and duration of cyanobacterial
blooms. Such blooms may cause fish kills, have adverse health effects on humans and contribute to the loss of biodiversity
in aquatic ecosystems. Some 50 eutrophic to hypereutrophic ponds from the Brussels Capital Region (Belgium) were studied between
2003 and 2009. A number of the ponds studied are prone to persistent cyanobacterial blooms. Because of the related health
concerns and adverse effects on ecological quality of the affected ponds, a tool for assessment of the risk of cyanobacterial
bloom occurrence was needed. The data acquired showed that cyanobacteria have threshold relationships with most of the environmental
factors that control them. This is negatively reflected on the predictive capacity of conventional statistical methods based
on linear relationships. Therefore, classification trees designed for the treatment of complex data and non-linear relationships
were used to assess the risk of cyanobacterial bloom occurrence. The main factors determining cyanobacterial bloom development
appeared to be phytoplankton biomass, pH and, to a lesser degree, nitrogen availability. These results suggest that to outcompete
eukaryotic phytoplankters cyanobacteria need the presence of environmental constraints: carbon limitation, light limitation
and nitrogen limitation, for which they developed a number of adaptations. In the absence of constraints, eukaryotic phytoplankters
appear to be more competitive. Therefore, prior build up of phytoplankton biomass seems to be essential for cyanobacterial
dominance. Classification trees proved to be an efficient tool for the bloom risk assessment and allowed the main factors
controlling bloom development to be identified as well as the risk of bloom occurrence corresponding to the conditions determined
by these factors to be quantified. The results produced by the classification trees are consistent with those obtained earlier
by probabilistic approach to bloom risk assessment. They can facilitate planning management interventions and setting restoration
priorities. 相似文献
90.
Akushevich I Veremeyeva G Kravchenko J Ukraintseva S Arbeev K Akleyev AV Yashin AI 《Mathematical biosciences》2012,236(1):16-30
In this paper we present a new multiple-pathway stochastic model of carcinogenesis with potential of predicting individual incidence risks on the basis of biomedical measurements. The model incorporates the concept of intracellular barrier mechanisms in which cell malignization occurs due to an inefficient operation of barrier cell mechanisms, such as antioxidant defense, repair systems, and apoptosis. Mathematical formalism combines methodological innovations of mechanistic carcinogenesis models and stochastic process models widely used in studying biodemography of aging and longevity. An advantage of the modeling approach is in the natural combining of two types of measures expressed in terms of model parameters: age-specific hazard rate and means of barrier states. Results of simulation studies allow us to conclude that the model parameters can be estimated in joint analyses of epidemiological data and newly collected data on individual biomolecular measurements of barrier states. Respective experimental designs for such measurements are suggested and discussed. An analytical solution is obtained for the simplest design when only age-specific incidence rates are observed. Detailed comparison with TSCE model reveals advantages of the approach such as the possibility to describe decline in risk at advanced ages, possibilities to describe heterogeneous system of intermediate cells, and perspectives for individual prognoses of cancer risks. Application of the results to fit the SEER data on cancer risks demonstrates a strong predictive power of the model. Further generalizations of the model, opportunities to measure barrier systems, biomedical and mathematical aspects of the new model are discussed. 相似文献