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Karin Schuster-Gossler Ralf Cordes Julia Müller Insa Geffers Patricia Delany-Heiken Manuel Taft Matthias Preller Achim Gossler 《Genetics》2016,202(3):1119-1133
The highly conserved Notch-signaling pathway mediates cell-to-cell communication and is pivotal for multiple developmental processes and tissue homeostasis in adult organisms. Notch receptors and their ligands are transmembrane proteins with multiple epidermal-growth-factor-like (EGF) repeats in their extracellular domains. In vitro the EGF repeats of mammalian ligands that are essential for Notch activation have been defined. However, in vivo the significance of the structural integrity of each EGF repeat in the ligand ectodomain for ligand function is still unclear. Here, we analyzed the mouse Notch ligand DLL1. We expressed DLL1 proteins with mutations disrupting disulfide bridges in each individual EGF repeat from single-copy transgenes in the HPRT locus of embryonic stem cells. In Notch transactivation assays all mutations impinged on DLL1 function and affected both NOTCH1 and NOTCH2 receptors similarly. An allelic series in mice that carried the same point mutations in endogenous Dll1, generated using a mini-gene strategy, showed that early developmental processes depending on DLL1-mediated NOTCH activation were differently sensitive to mutation of individual EGF repeats in DLL1. Notably, some mutations affected only somite patterning and resulted in vertebral column defects resembling spondylocostal dysostosis. In conclusion, the structural integrity of each individual EGF repeat in the extracellular domain of DLL1 is necessary for full DLL1 activity, and certain mutations in Dll1 might contribute to spondylocostal dysostosis in humans. 相似文献
3.
Metal clusters are ubiquitously used as electron-transfer (ET) agents in biology. Their presence raises the question of how
the polynuclear nature of these systems influences ET. In an earlier study, a theoretical model was formulated to describe
ET from a mixed-valence dimer to a diamagnetic acceptor. In the present work, this approach is generalized to analyze the
effect of valence delocalization on the rate of ET in a larger class of donor–acceptor systems. Our results indicate that
the effect of valence delocalization on ET rate depends on whether the mixed-valence (MV) state occurs in the initial or final
state of the reaction and on the reaction regime (normal vs inverted) as defined by Marcus. The analysis provides a possible
correlation between the rate constant for ET from CuA to heme a and the difference in the valence delocalization of the CuA centers in wild-type and mutant species of cytochrome c oxidase. We have analyzed the dependence of the electron flow through extended circuits containing MV clusters on valence
delocalization. A significant effect was found in the fast ET regime where the capacity of the circuit to conduct electrons
is optimally used. The possibility of controlling electron conduction by tuning valence delocalization is briefly addressed.
Received: 16 July 1997 / Accepted: 26 November 1997 相似文献
4.
Luc E. Coffeng Wilma A. Stolk Achim Hoerauf Dik Habbema Roel Bakker Adrian D. Hopkins Sake J. de Vlas 《PloS one》2014,9(12)
The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently. 相似文献
5.
6.
Achim Raab 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1970,68(3):272-275
Summary The present method permits rapid and sensitive study of the concentration levels of serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) in the same tissue sample and the determination of the turnover of these substances in small brain parts.I wish to thank Merck Sharp and Dohme for supplies of probenecid. 相似文献
7.
Overexpression of eCLCA1 in small airways of horses with recurrent airway obstruction. 总被引:1,自引:0,他引:1
Friederike Anton Ina Leverkoehne Lars Mundhenk Wallace B Thoreson Achim D Gruber 《The journal of histochemistry and cytochemistry》2005,53(8):1011-1021
The human hCLCA1 and murine mCLCA3 (chloride channels, calcium-activated) have recently been identified as promising therapeutic targets in asthma. Recurrent airway obstruction in horses is an important animal model of human asthma. Here, we have cloned and characterized the first equine CLCA family member, eCLCA1. The 913 amino acids eCLCA1 polypeptide forms a 120-kDa transmembrane glycoprotein that is processed to an 80-kDa protein in vivo. Three single nucleotide polymorphisms were detected in the eCLCA1 coding region in 14 horses, resulting in two amino acid changes (485H/R and 490V/L). However, no functional differences were recorded between the channel properties of the two variants in transfected HEK293 cells. The eCLCA1 protein was detected immunohistochemically in mucin-producing cells in the respiratory and intestinal tracts, cutaneous sweat glands, and renal mucous glands. Strong overexpression of eCLCA1 was observed in the airways of horses with recurrent airway obstruction using Northern blot hybridization, Western blotting, immunohistochemistry, and real-time quantitative RT-PCR. The results suggest that spontaneous or experimental recurrent airway obstruction in horses may serve as a model to study the role of CLCA homologs in chronic airway disease with overproduction of mucins. 相似文献
8.
Fourier Transform Infrared and Raman Spectroscopy for Characterization of Listeria monocytogenes Strains 总被引:1,自引:0,他引:1 下载免费PDF全文
Astrid Oust Trond Mretr Kristine Naterstad Ganesh D. Sockalingum Isabelle Adt Michel Manfait Achim Kohler 《Applied microbiology》2006,72(1):228-232
The purpose of this study was to characterize the variation in biochemical composition of 89 strains of Listeria monocytogenes with different susceptibilities towards sakacin P, using Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy. The strains were also analyzed using amplified fragment length polymorphism (AFLP) analysis. Based on their susceptibilities to sakacin P, the 89 strains have previously been divided into two groups. Using the FTIR spectra and AFLP data, the strains were basically differentiated into the same two groups. Analyses of the FTIR and Raman spectra revealed that the strains in the two groups contained differences in the compositions of carbohydrates and fatty acids. The relevance of the variation in the composition of carbohydrates with respect to the variation in the susceptibility towards sakacin P for the L. monocytogenes strains is discussed. 相似文献
9.
Marc Faget Kerstin A. Nagel Achim Walter Juan M. Herrera Siegfried Jahnke Ulrich Schurr Vicky M. Temperton 《Annals of botany》2013,112(2):253-266
Background
There is a large body of literature on competitive interactions among plants, but many studies have only focused on above-ground interactions and little is known about root–root dynamics between interacting plants. The perspective on possible mechanisms that explain the outcome of root–root interactions has recently been extended to include non-resource-driven mechanisms (as well as resource-driven mechanisms) of root competition and positive interactions such as facilitation. These approaches have often suffered from being static, partly due to the lack of appropriate methodologies for in-situ non-destructive root characterization.Scope
Recent studies show that interactive effects of plant neighbourhood interactions follow non-linear and non-additive paths that are hard to explain. Common outcomes such as accumulation of roots mainly in the topsoil cannot be explained solely by competition theory but require a more inclusive theoretical, as well as an improved methodological framework. This will include the question of whether we can apply the same conceptual framework to crop versus natural species.Conclusions
The development of non-invasive methods to dynamically study root–root interactions in vivo will provide the necessary tools to study a more inclusive conceptual framework for root–root interactions. By following the dynamics of root–root interactions through time in a whole range of scenarios and systems, using a wide variety of non-invasive methods, (such as fluorescent protein which now allows us to separately identify the roots of several individuals within soil), we will be much better equipped to answer some of the key questions in root physiology, ecology and agronomy. 相似文献10.
Nina M. Pollak Martina Schweiger Doris Jaeger Dagmar Kolb Manju Kumari Renate Schreiber Stephanie Kolleritsch Philipp Markolin Gernot F. Grabner Christoph Heier Kathrin A. Zierler Thomas Rülicke Robert Zimmermann Achim Lass Rudolf Zechner Guenter Haemmerle 《Journal of lipid research》2013,54(4):1092-1102
Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL and its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 expression increases cellular TG content and Plin5-deficient mice exhibit reduced cardiac TG levels. In this study we show that mice with cardiac muscle-specific overexpression of perilipin 5 (CM-Plin5) massively accumulate TG in CM, which is accompanied by moderately reduced fatty acid (FA) oxidizing gene expression levels. Cardiac lipid droplet (LD) preparations from CM of CM-Plin5 mice showed reduced ATGL- and hormone-sensitive lipase-mediated TG mobilization implying that Plin5 overexpression restricts cardiac lipolysis via the formation of a lipolytic barrier. To test this hypothesis, we analyzed TG hydrolytic activities in preparations of Plin5-, ATGL-, and CGI-58-transfected cells. In vitro ATGL-mediated TG hydrolysis of an artificial micellar TG substrate was not inhibited by the presence of Plin5, whereas Plin5-coated LDs were resistant toward ATGL-mediated TG catabolism. These findings strongly suggest that Plin5 functions as a lipolytic barrier to protect the cardiac TG pool from uncontrolled TG mobilization and the excessive release of free FAs. 相似文献