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481.
Research on phenotypic plasticity has often focused on how a given genotype responds to the changing physical environments such as temperature or diet. However, for many species the social environment has an equally important role because of competition for resources. During early development, the level of competition for limited (maternally provided) resources will often depend critically on the number of siblings. Therefore, competition among siblings should drive the evolution of genes that allow flexible responses to realized levels of competition and maternal resource availability. However, it is unknown whether genetically based differences between individuals exist in their response to the social environment that affect their future development. Using a quantitative trait locus approach in an experimental population of mice we demonstrate that effects of sibling number on body weight depend on individual genotype at seven loci, over and above the general negative litter size effect. Overall, these litter size-by-genotype interactions considerably modified the degree to which increasing litter size caused reduced weight. For example at one locus this effect leads to a 7% difference in body weight at week 7 between individuals experiencing the extremes of the normal range of litter sizes in our population (five to nine litter mates). The observed interaction between genotype and the competitive environment can produce differences in body weight that are similar in magnitude to the main effect of litter size on weight. Our results show that different genotypes respond to the social environment differentially and that interaction effects of genotype with litter size can be as important as genotype-independent effects of litter size. 相似文献
482.
H Hooton L Angquist C Holst J Hager F Rousseau RD Hansen A Tjønneland N Roswall DL van der A K Overvad MU Jakobsen H Boeing K Meidtner D Palli G Masala N Bouatia-Naji WH Saris EJ Feskens NJ Wareham KS Vimaleswaran D Langin RJ Loos TI Sørensen K Clément 《PloS one》2012,7(7):e40394
Background/Aims
Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology–this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced by dietary factors–increased by high protein, glycemic index and energy diets.Methods
Four tag SNPs (rs7511673, rs11576175, rs10888390 and rs1136774) were selected to capture all common variation in the CTSS region. Association between these four SNPs and several adiposity measurements (BMI, waist circumference, waist for given BMI and being a weight gainer–experiencing the greatest degree of unexplained annual weight gain during follow-up or not) given, where applicable, both as baseline values and gain during the study period (6–8 years) were tested in 11,091 European individuals (linear or logistic regression models). We also examined the interaction between the CTSS variants and dietary factors–energy density, protein content (in grams or in % of total energy intake) and glycemic index–on these four adiposity phenotypes.Results
We found several associations between CTSS polymorphisms and anthropometric traits including baseline BMI (rs11576175 (SNP N°2), p = 0.02, β = −0.2446), and waist change over time (rs7511673 (SNP N°1), p = 0.01, β = −0.0433 and rs10888390 (SNP N°3), p = 0.04, β = −0.0342). In interaction with the percentage of proteins contained in the diet, rs11576175 (SNP N°2) was also associated with the risk of being a weight gainer (pinteraction = 0.01, OR = 1.0526)–the risk of being a weight gainer increased with the percentage of proteins contained in the diet.Conclusion
CTSS variants seem to be nominally associated to obesity related traits and this association may be modified by dietary protein intake. 相似文献483.
Pablo H. Sotelo Noberto Collazo Roberto Zu?iga Matías Gutiérrez-González Diego Catalán Carolina Hager Ribeiro Juan Carlos Aguillón María Carmen Molina 《MABS-AUSTIN》2012,4(4):542-550
Phage display library technology is a common method to produce human antibodies. In this technique, the immunoglobulin variable regions are displayed in a bacteriophage in a way that each filamentous virus displays the product of a single antibody gene on its surface. From the collection of different phages, it is possible to isolate the virus that recognizes specific targets. The most common form in which to display antibody variable regions in the phage is the single chain variable fragment format (scFv), which requires assembly of the heavy and light immunoglobulin variable regions in a single gene.
In this work, we describe a simple and efficient method for the assembly of immunoglobulin heavy and light chain variable regions in a scFv format. This procedure involves a two-step reaction: (1) DNA amplification to produce the single strand form of the heavy or light chain gene required for the fusion; and (2) mixture of both single strand products followed by an assembly reaction to construct a complete scFv gene. Using this method, we produced 6-fold more scFv encoding DNA than the commonly used splicing by overlap extension PCR (SOE-PCR) approach. The scFv gene produced by this method also proved to be efficient in generating a diverse scFv phage display library. From this scFv library, we obtained phages that bound several non-related antigens, including recombinant proteins and rotavirus particles. 相似文献
484.
Denisov IG Dawson JH Hager LP Sligar SG 《Biochemical and biophysical research communications》2007,363(4):954-958
The hydroperoxo-ferric complex, or Compound 0 (Cpd 0), is an unstable transient intermediate common for oxygen activating heme enzymes such as the cytochromes P450, nitric oxide synthases, and heme oxygenases, as well as the peroxidases and catalases which utilize hydrogen peroxide as a source of oxygen and reducing equivalents. Detailed understanding of the mechanism of oxygen activation and formation of the higher valent catalytically active intermediates in heme enzyme catalysis requires the structural and spectroscopic characterization of this immediate precursor, Cpd 0. Using the method of cryoradiolytic reduction of the oxy-ferrous heme complex, we have prepared and characterized hydroperoxo-ferric complex in chloroperoxidase (CPO) and compared this to the same intermediate generated in cytochrome P450 CYP101. Optical absorption spectrum of Cpd 0 in CPO has a Soret band at 449 nm and poorly resolved α, β bands at 576 and 546 nm. 相似文献
485.
486.
487.
Kim Dongjin Hager Megan Brant Eleanor Budak Hikmet 《Functional & integrative genomics》2021,21(3-4):355-366
Functional & Integrative Genomics - Genome editing can be used to create new wheat varieties with enhanced performance. Clustered regularly interspaced short palindromic repeat (CRISPR) is a... 相似文献
488.
Knecht W Willemse J Stenhamre H Andersson M Berntsson P Furebring C Harrysson A Hager AC Wissing BM Hendriks D Cronet P 《The FEBS journal》2006,273(4):778-792
Procarboxypeptidase U [proCPU, thrombin-activatable fibrinolysis inhibitor (TAFI), EC 3.4.17.20] belongs to the metallocarboxypeptidase family and is a zymogen found in human plasma. ProCPU has been proposed to be a molecular link between coagulation and fibrinolysis. Upon activation of proCPU, the active enzyme (CPU) rapidly becomes inactive due to its intrinsic instability. The inherent instability of CPU is likely to be of major importance for the in vivo down-regulation of its activity, but the underlying structural mechanisms of this fast and spontaneous loss of activity of CPU have not yet been explained, and they severely inhibit the structural characterization of CPU. In this study, we screened for more thermostable versions of CPU to increase our understanding of the mechanism underlying the instability of CPU's activity. We have shown that single as well as a few 2-4 mutations in human CPU can prolong the half-life of CPU's activity at 37 degrees C from 0.2 h of wild-type CPU to 0.5-5.5 h for the mutants. We provide evidence that the gain in stable activity is accompanied by a gain in thermostability of the enzyme and increased resistance to proteolytic digest by trypsin. Using one of the stable mutants, we demonstrate the importance of CPU stability over proCPU concentration in down-regulating fibrinolysis. 相似文献
489.
Xinle Wu Hongfei Ge Bryan Lemon Steven Vonderfecht Jennifer Weiszmann Randy Hecht Jamila Gupte Todd Hager Zhulun Wang Richard Lindberg Yang Li 《The Journal of biological chemistry》2010,285(8):5165-5170
FGF19 and FGF21, unique members of the fibroblast growth factor (FGF) family, are hormones that regulate glucose, lipid, and energy homeostasis. Increased hepatocyte proliferation and liver tumor formation have also been observed in FGF19 transgenic mice. Here, we report that, in contrast to FGF19, FGF21 does not induce hepatocyte proliferation in vivo. To identify the mechanism for FGF19-induced hepatocyte proliferation, we explored similarities and differences in receptor specificity between FGF19 and FGF21. We find that although both are able to activate FGF receptors (FGFRs) 1c, 2c, and 3c, only FGF19 activates FGFR4, the predominant receptor in the liver. Using a C-terminal truncation mutant of FGF19 and a series of FGF19/FGF21 chimeric molecules, we determined that amino acids residues 38–42 of FGF19 are sufficient to confer both FGFR4 activation and increased hepatocyte proliferation in vivo to FGF21. These data suggest that activation of FGFR4 is the mechanism whereby FGF19 can increase hepatocyte proliferation and induce hepatocellular carcinoma formation. 相似文献
490.
The first responses in spruce [Picea abies (L.) Karst.] cells induced by elicitors (N-acetylglucosamine oligomers) from ectomycorrhizal fungi have been described as
follows: efflux of Cl− and K+, influx of Ca2+, extracellular alkalinization, phosphorylation of a 63-kDa protein (pp63), dephosphorylation of a 65-kDa protein (pp65) and
synthesis of H2O2 (Salzer et al. 1996, Planta 198: 118–126). In order to obtain new insights into the triggering mechanism and the sequence
of these rapid responses we used compounds which are known to activate or block specific steps within an elicitor-induced
signal transduction cascade in plant cells. Comparable to elicitors the two protein phosphatase inhibitors, cantharidin and
calyculin A, as well as mastoparan, an activator of trimeric G-proteins, were able to induce the release of Cl− and K+ from spruce cells and the alkalinization of the medium. Half-maximal activation of the alkalinization occurred at 133 nM
calyculin A, 2.3 μM cantharidin and 1.6 μ mastoparan. The structural analogue of mastoparan, Mas 17, which has no G-protein-stimulating
properties, was unable to trigger the above-mentioned reactions. In addition, cantharidin and calyculin A induced an increased
synthesis of H2O2 in spruce cells which was prolonged in comparison to the elicitor-induced transient formation of H2O2. Also, the cantharidin-induced release of K+ was more pronounced and longer lasting than that caused by elicitors from the ectomycorrhizal fungus Hebeloma crustuliniforme (Bull. ex Fries.) and N-acetylglucosamine oligomers. Furthermore, cantharidin, calyculin A and mastoparan induced the phosphorylation
of pp63. Remarkably, the protein kinase inhibitor, staurosporine, inhibited all the rapid responses described above, no matter
whether they were triggered by fungal elicitors or by the protein phosphatase inhibitors. These results indicate that in the
initial signalling events in spruce cells, essential protein phosphorylations occur either as an (auto) phosphorylation of
a membrane-bound receptor kinase prior to the activation of a G-protein or (and) immediately downstream of the activated G-protein
in a phosphorylation cascade and are the basic requirements for the ion fluxes following downstream.
Received: 24 April 1998 / Accepted: 23 July 1998 相似文献