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81.
A major challenge in designing proteins de novo to bind user-defined ligands with high affinity is finding backbones structures into which a new binding site geometry can be engineered with high precision. Recent advances in methods to generate protein fold families de novo have expanded the space of accessible protein structures, but it is not clear to what extend de novo proteins with diverse geometries also expand the space of designable ligand binding functions. We constructed a library of 25,806 high-quality ligand binding sites and developed a fast protocol to place (“match”) these binding sites into both naturally occurring and de novo protein families with two fold topologies: Rossman and NTF2. Each matching step involves engineering new binding site residues into each protein “scaffold”, which is distinct from the problem of comparing already existing binding pockets. 5,896 and 7,475 binding sites could be matched to the Rossmann and NTF2 fold families, respectively. De novo designed Rossman and NTF2 protein families can support 1,791 and 678 binding sites that cannot be matched to naturally existing structures with the same topologies, respectively. While the number of protein residues in ligand binding sites is the major determinant of matching success, ligand size and primary sequence separation of binding site residues also play important roles. The number of matched binding sites are power law functions of the number of members in a fold family. Our results suggest that de novo sampling of geometric variations on diverse fold topologies can significantly expand the space of designable ligand binding sites for a wealth of possible new protein functions. 相似文献
82.
Our study was designed to evaluate if, and to what extent, restrictive environmental conditions affect otolith morphology. As a model, we chose two extremophile livebearing fishes: (i) Poecilia mexicana, a widespread species in various Mexican freshwater habitats, with locally adapted populations thriving in habitats characterized by the presence of one (or both) of the natural stressors hydrogen sulphide and darkness, and (ii) the closely related Poecilia sulphuraria living in a highly sulphidic habitat (Baños del Azufre). All three otolith types (lapilli, sagittae, and asterisci) of P. mexicana showed a decrease in size ranging from the non-sulphidic cave habitat (Cueva Luna Azufre), to non-sulphidic surface habitats, to the sulphidic cave (Cueva del Azufre), to sulphidic surface habitats (El Azufre), to P. sulphuraria. Although we found a distinct differentiation between ecotypes with respect to their otolith morphology, no clear-cut pattern of trait evolution along the two ecological gradients was discernible. Otoliths from extremophiles captured in the wild revealed only slight similarities to aberrant otoliths found in captive-bred fish. We therefore hypothesize that extremophile fishes have developed coping mechanisms enabling them to avoid aberrant otolith growth – an otherwise common phenomenon in fishes reared under stressful conditions. 相似文献
83.
Biotechnologically produced succinic acid has the potential to displace maleic acid and its uses and to become an important
feedstock for the chemical industry. In addition to optimized production strains and fermentation processes, an efficient
separation of succinic acid from the aqueous fermentation broth is indispensable to compete with the current petrochemical
production processes. In this context, high molecular weight amines are known to be effective extractants for organic acids.
For this reason, as a first step of isolation and purification, the reactive extraction of succinic acid was studied by mixing
aqueous succinic acid solutions with 448 different amine–solvent mixtures as extraction agents (mixer-settler studies). The
extraction agents consist either of one amine and one solvent (208 reactive extraction systems) or two amines and two solvents
(240 reactive extraction systems). Maximum extraction yields of succinic acid from an aqueous solution with 423 mM succinic
acid at pH 2.0 were obtained with more than 95% yield with trihexylamine solved in 1-octanol or with dihexylamine and diisooctylamine
solved in 1-octanol and 1-hexanol. Applying these optimized reactive extraction systems with Escherichia coli fermentation broth resulted in extraction yields of 78–85% due to the increased ionic strength of the fermentation supernatant
and the co-extraction of other organic acids (e.g., lactic acid and acetic acid), which represent typical fermentation byproducts. 相似文献
84.
A series of recent papers highlight a prominent role for ubiquitin in the formation and function of neural circuits. These new results focus attention on the molecular remodeling that occurs at various decision points in the life of growth cones and synapses. 相似文献
85.
Tanja Adna?evi? Vladimir M. Jovanovi? Jelena Blagojevi? Ivana Budinski Borislav ?abrilo Olivera Bijeli?-?abrilo Mladen Vujo?evi? 《PloS one》2014,9(11)
Genetic background underlying wild populations immune response to different parasites is still not well understood. We studied immune response to multiple infections and to competition between different parasite species at different developmental stages in population of yellow-necked mouse, Apodemus flavicollis. Quantitative real-time PCR was used to investigate associations of MHC II-DRB, IL-10 and Tgf-β genes expressions with presence of intestinal parasites at different developmental stages. Furthermore, we were interested whether the host related characteristics (sex, age, body condition, presence of B chromosomes or expression of other genes) or characteristics of present parasites (number of adult parasites of each identified species, egg count of each parasite genus, total number of nematode individuals) affect differential expression of the studied genes. A significant invert association between the expression of MHC II-DRB and Tgf-β gene was found, which together with absence of IL-10 association confirmed modified Th2 as the main type of immune response to nematode infections. Effect of recorded parasites and parasite life-cycle stage on expression levels of MHC II-DRB gene was detected only through interactions with host-related characteristics such as sex, age, and the presence of B chromosomes. The presence of B chromosomes is associated with lower expression level of Tgf-β gene. Although the influence of host genetic background on parasite infection has already been well documented, this is the first study in mammals that gave presence of B chromosomes on immune response full consideration. 相似文献
86.
Arnold F Schnell J Zirafi O Stürzel C Meier C Weil T Ständker L Forssmann WG Roan NR Greene WC Kirchhoff F Münch J 《Journal of virology》2012,86(2):1244-1249
Semen is the major vector for HIV-1 transmission. We previously isolated C-proximal fragments of the prostatic acid phosphatase (PAP) from semen which formed amyloid fibrils that potently enhanced HIV infection. Here, we used the same methodology and identified another amyloidogenic peptide. Surprisingly, this peptide is derived from an N-proximal fragment of PAP (PAP85-120) and forms, similar to the C-proximal fragments, positively charged fibrillar structures that increase virion attachment to cells. Our results provide a first example for amyloid formation by fragments of distinct regions of the same precursor and further emphasize the possible importance of amyloidogenic peptides in HIV transmission. 相似文献
87.
Birgit Sklorz und Tanja Volz 《Journal of Ornithology》1990,131(2):157-160
Zusammenfassung Frisch geschlüpften Hühnerküken wurden schwarz-gelb geringelte und grüne Attrappen sowie Mehlwürmer angeboten, um zu testen, ob eine angeborene Hemmung gegenüber warnfarbiger Beute besteht. Unsere Küken zeigten sowohl eine eindeutige Präferenz für schwarzgelb geringelte Attrappen als auch für Mehlwürmer. Daraus schließen wir, daß es keine genetisch fixierte Hemmung gegenüber schwarz-gelber Ringelung, d. h. auffälliger Beute gibt.
Innate and learned preferences in food selection of chicken (Gallus domesticus)
Summary In reference to the experiment ofSchuler &Hesse (1985), recently hatched chicken were offered a choise between warningly coloured black and yellow and nonwarningly coloured green prey. We can not support their hypothesis of a genetically fixed pecking inhibition towards prey with warning colouration. The chicken directed their first peck at the warningly coloured ones and they ate them at a significantly higher rate. These results support the idea ofGittleman &Harvey (1980), that chicken prefer conspicuous prey.相似文献
88.
1 Laboratory studies demonstrated that the susceptibility of larvae of the lepidopteran crucifer pest Plutella xylostella to the insect pathogen Bacillus thuringiensis (Bt) was influenced by the host plant. 2 Larvae reared on the resistant cabbage cultivars Minicole F1 and Red Drumhead were significantly more susceptible to Bt (the LC50 fell to one half) than larvae fed leaves of susceptible cultivars. 3 However, a third resistant cultivar, Aquarius F1, had no synergistic effect on Bt‐related mortality. 4 Actual uptake of Bt was monitored in the bioassays, as a preliminary experiment showed that the plant resistance reduced consumption of Bt‐treated leaf discs. However, differences in feeding rate did not explain the observed differences in mortality. 相似文献
89.
Behrmann I Smyczek T Heinrich PC Schmitz-Van de Leur H Komyod W Giese B Müller-Newen G Haan S Haan C 《The Journal of biological chemistry》2004,279(34):35486-35493
The Janus kinases are considered to be cytoplasmic kinases that constitutively associate with the cytoplasmic region of cytokine receptors, and the Janus kinases (Jaks) are crucial for cytokine signal transduction. We investigated Jak1 localization using subcellular fractionation techniques and fluorescence microscopy (immunofluorescence and yellow fluorescent protein-tagged Jaks). In the different experimental approaches we found Jak1 (as well as Jak2 and Tyk2) predominantly located at membranes. In contrast to previous reports we did not observe Jak proteins in significant amounts within the nucleus or in the cytoplasm. The cytoplasmic localization observed for the Jak1 mutant L80A/Y81A, which is unable to associate with cytokine receptors, indicates that Jak1 does not have a strong intrinsic membrane binding potential and that only receptor binding is crucial for the membrane recruitment. Finally we show that Jak1 remains a membrane-localized protein after cytokine stimulation. These data strongly support the hypothesis that cytokine receptor.Janus kinase complexes can be regarded as receptor tyrosine kinases. 相似文献
90.
Sophie Garnier Vinh Truong Jessy Brocheton Tanja Zeller Maxime Rovital Philipp S. Wild Andreas Ziegler The Cardiogenics Consortium Thomas Munzel Laurence Tiret Stefan Blankenberg Panos Deloukas Jeannette Erdmann Christian Hengstenberg Nilesh J. Samani Heribert Schunkert Willem H. Ouwehand Alison H. Goodall Fran?ois Cambien David-Alexandre Trégou?t 《PLoS genetics》2013,9(1)