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991.
Hua QX Nakagawa S Hu SQ Jia W Wang S Weiss MA 《The Journal of biological chemistry》2006,281(34):24900-24909
How insulin binds to the insulin receptor has long been a subject of speculation. Although the structure of the free hormone has been extensively characterized, a variety of evidence suggests that a conformational change occurs upon receptor binding. Here, we employ chiral mutagenesis, comparison of corresponding d and l amino acid substitutions, to investigate a possible switch in the B-chain. To investigate the interrelation of structure, function, and stability, isomeric analogs have been synthesized in which an invariant glycine in a beta-turn (Gly(B8)) is replaced by d- or l-Ser. The d substitution enhances stability (DeltaDeltaG(u) 0.9 kcal/mol) but impairs receptor binding by 100-fold; by contrast, the l substitution markedly impairs stability (DeltaDeltaG(u) -3.0 kcal/mol) with only 2-fold reduction in receptor binding. Although the isomeric structures each retain a native-like overall fold, the l-Ser(B8) analog exhibits fewer helix-related and long range nuclear Overhauser effects than does the d-Ser(B8) analog or native monomer. Evidence for enhanced conformational fluctuations in the unstable analog is provided by its attenuated CD spectrum. The inverse relationship between stereospecific stabilization and receptor binding strongly suggests that the B7-B10 beta-turn changes conformation on receptor binding. 相似文献
992.
993.
In cDNA microarray image processing, there are different methods for calculating the channel ratios. Standard microarray image analysis software, such as the Axon GenePix® Pro, calculate the channel ratio from pixels that define a given spot using different methods (i.e. ratio of means, ratio of medians, mean of ratios, median of ratios, and regression ratio). Ratio values calculated using the different methods will then be listed in an output file. Microarray users have to choose one of the available methods at their own discretion, as no guidelines are provided. Therefore, we aim to address one of the most frequently asked questions by the microarray users: which ratio quantity provided by the image analysis software should be used? In this study, we have evaluated the five different ratio calculation approaches using simulation studies. Our results suggest that in most circumstances the ratio of means appears to be the best approach, particularly when the coefficient of variance (CV) of two-channel pixel intensities are small (<0.5) and channel intensities are large. Conversely, the ratio of medians and the median of ratios are more favourable when the CV is large. 相似文献
994.
Genetic Diversity and Core Collection Evaluations in Common Wheat Germplasm from the Northwestern Spring Wheat Region in China 总被引:6,自引:0,他引:6
C. Y. Hao X. Y. Zhang L. F. Wang Y. S. Dong X. W. Shang J. Z. Jia 《Molecular breeding : new strategies in plant improvement》2006,17(1):69-77
Fluorescence microsatellite markers were employed to reveal genetic diversity of 340 wheat accessions consisting of 229 landraces
and 111 modern varieties from the Northwest Spring Wheat Region in China. The 340 accessions were chosen as candidate core
collections for wheat germplasm in this region. A core collection representing the genetic diversity of these accessions was
identified based on a cluster dendrogram of 78 SSR loci. A total of 967 alleles were detected with a mean of 13.6 alleles
(5–32) per locus. Mean PIC was 0.64, ranged from 0.05 to 0.91. All loci were distributed relatively evenly in the A, B and
D wheat genomes. Mean genetic richness of A, B and D genomes for both landraces and modern varieties was B > A > D. However,
mean genetic diversity indices of landraces changed to B > D > A. As a whole, genetic diversity of the landraces was considerably
higher than that of the modern varieties. The big difference of genetic diversity indices in the three genomes suggested that
breeding has exerted greater selection pressure in the D than the A or B genomes in this region. Changes of allelic proportions
represented in the proposed core collection at different sampling scales suggested that the sampling percentage of the core
collection in the Northwest Spring Wheat Region should be greater than 4% of the base collection to ensure that more than
70% of the variation is represented by the core collection.
Electronic supplementary material Electronic supplementary material is available for this article at
and accessible for authorised users. 相似文献
995.
While providing nearly trouble-free function for 10-12 years, current bioprosthetic heart valves (BHV) continue to suffer from limited long-term durability. This is usually a result of leaflet calcification and/or structural degeneration, which may be related to regions of stress concentration associated with complex leaflet deformations. In the current work, a dynamic three-dimensional finite element analysis of a pericardial BHV was performed with a recently developed FE implementation of the generalized nonlinear anisotropic Fung-type elastic constitutive model for pericardial BHV tissues (W. Sun and M.S. Sacks, 2005, [Biomech. Model. Mechanobiol., 4(2-3), pp. 190-199]). The pericardial BHV was subjected to time-varying physiological pressure loading to compute the deformation and stress distribution during the opening phase of the valve function. A dynamic sequence of the displacements revealed that the free edge of the leaflet reached the fully open position earlier and the belly region followed. Asymmetry was observed in the resulting displacement and stress distribution due to the fiber direction and the anisotropic characteristics of the Fung-type elastic constitutive material model. The computed stress distribution indicated relatively high magnitudes near the free edge of the leaflet with local bending deformation and subsequently at the leaflet attachment boundary. The maximum computed von Mises stress during the opening phase was 33.8 kPa. The dynamic analysis indicated that the free edge regions of the leaflets were subjected to significant flexural deformation that may potentially lead to structural degeneration after millions of cycles of valve function. The regions subjected to time varying flexural deformation and high stresses of the present study also correspond to regions of tissue valve calcification and structural failure reported from explanted valves. In addition, the present simulation also demonstrated the importance of including the bending component together with the in-plane material behavior of the leaflets towards physiologically realistic deformation of the leaflets. Dynamic simulations with experimentally determined leaflet material specification can be potentially used to modify the valve towards an optimal design to minimize regions of stress concentration and structural failure. 相似文献
996.
Apelin protects myocardial injury induced by isoproterenol in rats 总被引:16,自引:0,他引:16
Jia YX Pan CS Zhang J Geng B Zhao J Gerns H Yang J Chang JK Tang CS Qi YF 《Regulatory peptides》2006,133(1-3):147-154
We aimed to explore the change in level of apelin and its receptor APJ during myocardial injury and the therapeutic effects of apelin in myocardial injury. Rat myocardial injury was induced by subcutaneous injection of a high dose of isoproterenol (ISO); apelin and APJ mRNA levels were determined by RT-PCR; APJ protein was determined by Western blot; EIA and RIA were used to measure the apelin content and receptor binding, respectively. Plasma lactate dehydrogenase (LDH) activity and myocardial and plasma malondialdehyde (MDA) contents were higher in ISO-treated hearts than that in controls. ISO-treated rats showed lower +/-LV dp/dt(max) values and higher LVEDP value (all P<0.01), which suggested severe heart failure. As well, the apelin content in plasma, atrial and ventricular myocardium was decreased by 27%, 30% and 25% (P<0.01), respectively. The mRNA levels of apelin and APJ in myocardia were also markedly reduced; but the APJ protein level in myocardia was increased. However, administration of apelin significantly ameliorated myocardial injury and ISO-induced heart failure. Compared with the ISO-alone group, the group given low-dosage apelin (5 nmol/kg/day) had 39% and 66% higher +LV dp/dt(max) and -LV dp/dt(max) values, and 40.7% lower LVEDP value (P<0.01), and the leakage of myocardial LDH and increased MDA content were attenuated (all P<0.01). Interestingly, bolus injections of apelin (10 nmol/kg/day) resulted in potent inotropic effects in ISO-treated rats. ISO-induced myocardial injury resulted in hypoexpression of apelin and its receptor APJ, and the administration of exogenous apelin ameliorated heart failure and myocardial injury. Apelin could have a cardioprotective effect, and the apelin-APJ system may be a new therapeutic target in myocardial injury and heart failure. 相似文献
997.
998.
HACN (homoaconitase) is a member of a family of [4Fe-4S] cluster-dependent enzymes that catalyse hydration/dehydration reactions. The best characterized example of this family is the ubiquitous ACN (aconitase), which catalyses the dehydration of citrate to cis-aconitate, and the subsequent hydration of cis-aconitate to isocitrate. HACN is an enzyme from the alpha-aminoadipate pathway of lysine biosynthesis, and has been identified in higher fungi and several archaea and one thermophilic species of bacteria, Thermus thermophilus. HACN catalyses the hydration of cis-homoaconitate to (2R,3S)-homoisocitrate, but the HACN-catalysed dehydration of (R)-homocitrate to cis-homoaconitate has not been observed in vitro. We have synthesized the substrates and putative substrates for this enzyme, and in the present study report the first steady-state kinetic data for recombinant HACN from T. thermophilus using a (2R,3S)-homoisocitrate dehydrogenase-coupled assay. We have also examined the products of the reaction using HPLC. We do not observe HACN-catalysed 'homocitrate dehydratase' activity; however, we have observed that ACN can catalyse the dehydration of (R)-homocitrate to cis-homoaconitate, but HACN is required for subsequent conversion of cis-homoaconitate into homoisocitrate. This suggests that the in vivo process for conversion of homocitrate into homoisocitrate requires two enzymes, in simile with the propionate utilization pathway from Escherichia coli. Surprisingly, HACN does not show any activity when cis-aconitate is substituted for the substrate, even though other enzymes from the alpha-aminoadipate pathway can accept analogous tricarboxylic acid-cycle substrates. The enzyme shows no apparent feedback inhibition by L-lysine. 相似文献
999.
Our work has identified a cancer-specific, cell surface and growth-related quinol oxidase with both NADH oxidase and protein
disulfide-thiol interchange activities, a member of the ECTO-NOX protein family designated tNOX. We provide evidence for tNOX
as an alternative drug target to COX-2 to explain the anticancer activity of COX inhibitors. Non-steroidal anti-inflammatory
drugs (NSAIDS), piroxicam, aspirin, ibuprofen, naproxen and celecoxib all specifically inhibited tNOX activity of HeLa (human
cervical carcinoma) and BT-20 (human mammary carcinoma) cells (IC50 in the nanomolar range) without effect on ECTO-NOX activities of non-cancer MCF-10A mammary epithelial cells. With cancer
cells, rofecoxib was less effective and two NSAIDS selective for COX-1 were without effect in inhibiting NOX activity. The
IC50 for inhibition of tNOX activity of HeLa cells and the IC50 for inhibition of growth of HeLa cells in culture were closely correlated. The findings provide evidence for a new drug target
to account for anticancer effects of NSAIDS that occur independent of COX-2. 相似文献