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51.
Durany O Bassett P Weiss AM Cranenburgh RM Ferrer P López-Santín J de Mas C Hanak JA 《Biotechnology and bioengineering》2005,91(4):460-467
We report a novel application for the operator-repressor titration (ORT) plasmid maintenance system. The ability of ORT to maintain a plasmid during production of DNA has been demonstrated previously. In this study, we have used the ORT system to maintain a plasmid during high cell density cultivation and expression of a recombinant protein. No evidence of plasmid loss was seen during protein expression at high cell densities. In addition, the quantity of protein produced using this system was similar to traditional plasmid maintenance systems. 相似文献
52.
Bernard F. Hoskins Anthony Linden Pau.C. Mulvaney Thomas A. ODonnell 《Inorganica chimica acta》1984,88(2):217-222
The crystal structure of CsReF6, together with a reinvestigation of that of BaSiF6, is reported. Both have been determined from single crystal three-dimensional X-ray diffraction data. The structure of BaSiF6 has been found to conform to the initially assigned space group Rm, contrary to the suggestions of other workers. The unit cell of BaSiF6 has the dimensiona ahex 7.189(1), chex 7.015(1) Å; Z = 3. Refinement by a least squares method gave R 0.0079 and Rw 0.0077. Crystals of CsReF6 belong to the lower symmetry rhombohedral space group R. The unit cell has the dimensions ahex 7.853(1), chex 8.140(1) Å; Z = 3. Refinement gave R 0.031 and Rw 0.030. The lowering of symmetry is caused by rotation of the ReF6? octahedra about the 3-fold axis through each Re atom, causing CsReF6 to have the KOsF6 structure. 相似文献
53.
Carles Pons Marco D’Abramo Dmitri I. Svergun Pau Bernadó Juan Fernández-Recio 《Journal of molecular biology》2010,403(2):217-230
X-ray crystallography and NMR can provide detailed structural information of protein-protein complexes, but technical problems make their application challenging in the high-throughput regime. Other methods such as small-angle X-ray scattering (SAXS) are more promising for large-scale application, but at the cost of lower resolution, which is a problem that can be solved by complementing SAXS data with theoretical simulations. Here, we propose a novel strategy that combines SAXS data and accurate protein-protein docking simulations. The approach has been benchmarked on a large pool of known structures with synthetic SAXS data, and on three experimental examples. The combined approach (pyDockSAXS) provided a significantly better success rate (43% for the top 10 predictions) than either of the two methods alone. Further analysis of the influence of different docking parameters made it possible to increase the success rates for specific cases, and to define guidelines for improving the data-driven protein-protein docking protocols. 相似文献
54.
Sancho-Bru P Bataller R Colmenero J Gasull X Moreno M Arroyo V Brenner DA Ginès P 《American journal of physiology. Gastrointestinal and liver physiology》2006,291(5):G877-G884
Catecholamines participate in the pathogenesis of portal hypertension and liver fibrosis through alpha1-adrenoceptors. However, the underlying cellular and molecular mechanisms are largely unknown. Here, we investigated the effects of norepinephrine (NE) on human hepatic stellate cells (HSC), which exert vasoactive, inflammatory, and fibrogenic actions in the injured liver. Adrenoceptor expression was assessed in human HSC by RT-PCR and immunocytochemistry. Intracellular Ca2+ concentration ([Ca2+]i) was studied in fura-2-loaded cells. Cell contraction was studied by assessing wrinkle formation and myosin light chain II (MLC II) phosphorylation. Cell proliferation and collagen-alpha1(I) expression were assessed by [3H]thymidine incorporation and quantitative PCR, respectively. NF-kappaB activation was assessed by luciferase reporter gene and p65 nuclear translocation. Chemokine secretion was assessed by ELISA. Normal human livers expressed alpha(1A)-adrenoceptors, which were markedly upregulated in livers with advanced fibrosis. Activated human HSC expressed alpha(1A)-adrenoceptors. NE induced multiple rapid [Ca2+]i oscillations (Ca2+ spikes). Prazosin (alpha1-blocker) completely prevented NE-induced Ca2+ spikes, whereas propranolol (nonspecific beta-blocker) partially attenuated this effect. NE caused phosphorylation of MLC II and cell contraction. In contrast, NE did not affect cell proliferation or collagen-alpha1(I) expression. Importantly, NE stimulated the secretion of inflammatory chemokines (RANTES and interleukin-8) in a dose-dependent manner. Prazosin blocked NE-induced chemokine secretion. NE stimulated NF-kappaB activation. BAY 11-7082, a specific NF-kappaB inhibitor, blocked NE-induced chemokine secretion. We conclude that NE stimulates NF-kappaB and induces cell contraction and proinflammatory effects in human HSC. Catecholamines may participate in the pathogenesis of portal hypertension and liver fibrosis by targeting HSC. 相似文献
55.
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57.
Aurélie Joly-Amado Rapha?l G P Denis Julien Castel Amélie Lacombe Céline Cansell Claude Rouch Nadim Kassis Julien Dairou Patrice D Cani Renée Ventura-Clapier Alexandre Prola Melissa Flamment Fabienne Foufelle Christophe Magnan Serge Luquet 《The EMBO journal》2012,31(22):4276-4288
Obesity-related diseases such as diabetes and dyslipidemia result from metabolic alterations including the defective conversion, storage and utilization of nutrients, but the central mechanisms that regulate this process of nutrient partitioning remain elusive. As positive regulators of feeding behaviour, agouti-related protein (AgRP) producing neurons are indispensible for the hypothalamic integration of energy balance. Here, we demonstrate a role for AgRP-neurons in the control of nutrient partitioning. We report that ablation of AgRP-neurons leads to a change in autonomic output onto liver, muscle and pancreas affecting the relative balance between lipids and carbohydrates metabolism. As a consequence, mice lacking AgRP-neurons become obese and hyperinsulinemic on regular chow but display reduced body weight gain and paradoxical improvement in glucose tolerance on high-fat diet. These results provide a direct demonstration of a role for AgRP-neurons in the coordination of efferent organ activity and nutrient partitioning, providing a mechanistic link between obesity and obesity-related disorders. 相似文献
58.
Qian Zhang Cornelia Hunke Yin Hoe Yau Vernon Seow Sumarlin Lee Lukas Bahati Tanner Xue Li Guan Markus R. Wenk Guntur Fibriansah Pau Ling Chew Petra Kukkaro Goran Biukovi? Pei-Yong Shi Susana Geifman Shochat Gerhard Grüber Shee-Mei Lok 《The Journal of biological chemistry》2012,287(48):40525-40534
Newly assembled dengue viruses (DENV) undergo maturation to become infectious particles. The maturation process involves major rearrangement of virus surface premembrane (prM) and envelope (E) proteins. The prM-E complexes on immature viruses are first assembled as trimeric spikes in the neutral pH environment of the endoplasmic reticulum. When the virus is transported to the low pH environment of the exosomes, these spikes rearrange into dimeric structures, which lie parallel to the virus lipid envelope. The proteins involved in driving this process are unknown. Previous cryoelectron microscopy studies of the mature DENV showed that the prM-stem region (residues 111–131) is membrane-associated and may interact with the E proteins. Here we investigated the prM-stem region in modulating the virus maturation process. The binding of the prM-stem region to the E protein was shown to increase significantly at low pH compared with neutral pH in ELISAs and surface plasmon resonance studies. In addition, the affinity of the prM-stem region for the liposome, as measured by fluorescence correlation spectroscopy, was also increased when pH is lowered. These results suggest that the prM-stem region forms a tight association with the virus membrane and attracts the associated E protein in the low pH environment of exosomes. This will lead to the surface protein rearrangement observed during maturation. 相似文献
59.
Signaling mediated by the Delta/Notch system controls the process of lateral inhibition, known to regulate neurogenesis in metazoans. Lateral inhibition takes place in equivalence groups formed by cells having equal capacity to differentiate, and it results in the singling out of precursors, which subsequently become neurons. During normal development, areas of active neurogenesis spread through non-neurogenic regions in response to specific morphogens, giving rise to neurogenic wavefronts. Close contact of these wavefronts with non-neurogenic cells is expected to affect lateral inhibition. Therefore, a mechanism should exist in these regions to prevent disturbances of the lateral inhibitory process. Focusing on the developing chick retina, we show that Dll1 is widely expressed by non-neurogenic precursors located at the periphery of this tissue, a region lacking Notch1, lFng, and differentiation-related gene expression. We investigated the role of this Dll1 expression through mathematical modeling. Our analysis predicts that the absence of Dll1 ahead of the neurogenic wavefront results in reduced robustness of the lateral inhibition process, often linked to enhanced neurogenesis and the presence of morphological alterations of the wavefront itself. These predictions are consistent with previous observations in the retina of mice in which Dll1 is conditionally mutated. The predictive capacity of our mathematical model was confirmed further by mimicking published results on the perturbation of morphogenetic furrow progression in the eye imaginal disc of Drosophila. Altogether, we propose that Notch-independent Delta expression ahead of the neurogenic wavefront is required to avoid perturbations in lateral inhibition and wavefront progression, thus optimizing the neurogenic process. 相似文献
60.