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31.
Biotransformation of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide,a novel potent 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties: In vitro and in silico approach 下载免费PDF全文
Karolina Słoczyńska Katarzyna Wójcik‐Pszczoła Vittorio Canale Paweł Żmudzki Paweł Zajdel Elżbieta Pękala 《Journal of biochemical and molecular toxicology》2018,32(5)
The aim of the study was to investigate the metabolism of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide (PZ‐1150), a novel 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties, by the following three ways: in vitro with microsomes; in vitro employing Cunninghamella echinulata, and in silico using MetaSite. Biotransformation of PZ‐1150 with microsomes resulted in five metabolites, while transformation with C. echinulata afforded two metabolites. In both models, the predominant metabolite occurred due to hydroxylation of benzene ring. In silico data coincide with in vitro experiments, as three MetaSite metabolites matched compounds identified in microsomal samples. In human liver microsomes PZ‐1150 exhibited in vitro half‐life of 64 min, with microsomal intrinsic clearance of 54.1 μL/min/mg and intrinsic clearance of 48.7 mL/min/kg. Therefore, PZ‐1150 is predicted to be a high‐clearance agent. The study demonstrated the applicability of using microsomal model coupled with microbial model to elucidate the metabolic pathways of compounds and comparison with in silico metabolite predictions. 相似文献
32.
Effect of lead stress on mineral content and growth of wheat (Triticum aestivum) and spinach (Spinacia oleracea) seedlings 总被引:1,自引:0,他引:1
Mostafa Lamhamdi Ouiam El Galiou Ahmed Bakrim Juan Carlos Nóvoa-Muñoz Manuel Arias-Estévez Ahmed Aarab René Lafont 《Saudi Journal of Biological Sciences》2013,20(1):29-36
Lead (Pb) is the most common heavy metal contaminant in the environment. Pb is not an essential element for plants, but they absorb it when it is present in their environment, especially in rural areas when the soil is polluted by automotive exhaust and in fields contaminated with fertilizers containing heavy metal impurities. To investigate lead effects on nutrient uptake and metabolism, two plant species, spinach (Spinacia oleracea) and wheat (Triticum aestivum), were grown under hydroponic conditions and stressed with lead nitrate, Pb(NO3)2, at three concentrations (1.5, 3, and 15 mM).Lead is accumulated in a dose-dependent manner in both plant species, which results in reduced growth and lower uptake of all mineral ions tested. Total amounts and concentrations of most mineral ions (Na, K, Ca, P, Mg, Fe, Cu and Zn) are reduced, although Mn concentrations are increased, as its uptake is reduced less relative to the whole plant’s growth. The deficiency of mineral nutrients correlates in a strong decrease in the contents of chlorophylls a and b and proline in both species, but these effects are less pronounced in spinach than in wheat. By contrast, the effects of lead on soluble proteins differ between species; they are reduced in wheat at all lead concentrations, whereas they are increased in spinach, where their value peaks at 3 mM Pb.The relative lead uptake by spinach and wheat, and the different susceptibility of these two species to lead treatment are discussed. 相似文献
33.
Md. Aminul Hoque Atefeh Taherian Fard Mosfequr Rahman Omar Alattas Kohei Akazawa Amir Feisal Merican 《Biologia》2011,66(6):954-966
We conducted an integrated study of cell growth parameters, product formation, and the dynamics of intracellular metabolite concentrations using Escherichia coli with genes knocked out in the glycolytic and oxidative pentose phosphate pathway (PPP) for glucose catabolism. We investigated the same characteristics in the wild-type strain, using acetate or pyruvate as the sole carbon source. Dramatic effects on growth parameters and extracellular and intracellular metabolite concentrations were observed after blocking either glycolytic breakdown of glucose by inactivation of phosphoglucose isomerase (disruption of pgi gene) or pentose phosphate breakdown of glucose by inactivation of glucose-6-phosphate dehydrogenase (disruption of zwf gene). Reducing power (NADPH) was mainly produced through PPP when the pgi gene was knocked out, while NADPH was produced through the tricarboxylic acid (TCA) cycle by isocitrate dehydrogenase or NADP-linked malic enzyme when the zwf gene was knocked out. As expected, when the pgi gene was knocked out, intracellular concentrations of PPP metabolites were high and glycolytic and concentrations of TCA cycle pathway metabolites were low. In the zwf gene knockout, concentrations of PPP metabolites were low and concentrations of intracellular glycolytic and TCA cycle metabolites were high. 相似文献
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Summary A new form of ectodermal dysplasia was observed in two siblings, offspring of healthy non-consanguineous parents. The main findings in both children are: hypodontia, abnormally shaped teeth, scalp hypotrichosis, pili annulati, follicular hyperkeratosis on the trunk and limbs, intensified delineation and reticular hyperpigmentation of the nape, and hyperopia; one of the siblings also has astigmatism. As both patients have normal nails and are euhidrotic, this is an ectodermal dysplasia of the pilodental subgroup. The cause is probably genetic and autosomal-recessive inheritance is most likely. 相似文献
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Fabrice Touzain Erick Denamur Claudine Médigue Valérie Barbe Meriem El Karoui Marie-Agnès Petit 《Genome biology》2010,11(4):R45
Background
Analysis of large scale diversity in bacterial genomes has mainly focused on elements such as pathogenicity islands, or more generally, genomic islands. These comprise numerous genes and confer important phenotypes, which are present or absent depending on strains. We report that despite this widely accepted notion, most diversity at the species level is composed of much smaller DNA segments, 20 to 500 bp in size, which we call microdiversity. 相似文献38.
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Muhammad Aasim Muhammad H. Khan Inam U. Rahman Noor Shad Bibi Waqar Ali Nadir Z. Khan Abid A. Khan 《Biotechnology progress》2019,35(4):e2828
Hydrophobic interaction chromatography, an important and effective purification strategy, is generally used for the purification of variety of biomolecules. A basic understanding of the protein interaction behavior is required to effectively separate these biomolecules. A colloidal type extended Derjaguin, Landau, Verwey, and Overbeek calculations were utilized to study the interactions behavior of model proteins to commercially available hydrophobic chromatographic materials that is, Toyopearl Phenyl 650C and Toyopearl Butyl 650C. Physicochemical properties of selected model proteins were achieved by contact angle and zeta potential measurements. The contact angle of chromatographic materials used was achieved through sessile drop method on disrupted beads and capillary penetration method (CPM) on intact beads. The surface properties were further used to calculate the interactions of the proteins to chromatographic supports. The calculated secondary energy minimum of the proteins with the chromatographic materials (from the contact angle values determined through both methods can be correlated with the retention volumes from the real chromatography. The secondary energy minimum values are higher for each protein to the chromatographic materials calculated from the inputs derived through sessile drop method compared to CPM. For instance, immunoglobulin G has secondary energy minimum value of 0.17 kT compared to 0.11 kT, obtained through sessile drop method and CPM, respectively. Average relative values of the energy minimum calculated for all proteins are as 1.51 kT and 1.29 kT for Toyopearl Butyl 650C and Toyopearl Phenyl 650C, respectively, as a conversion factor for estimation of secondary energy minimum for both methods. 相似文献
40.
ABSTRACT: BACKGROUND: Electrical Impedance Tomography (EIT) is used as a fast clinical imaging technique formonitoring the health of the human organs such as lungs, heart, brain and breast. Eachpractical EIT reconstruction algorithm should be efficient enough in terms of convergencerate, and accuracy. The main objective of this study is to investigate the feasibility of preciseempirical conductivity imaging using a sinc-convolution algorithm in D-bar framework. METHODS: At the first step, synthetic and experimental data were used to compute an intermediate objectnamed scattering transform. Next, this object was used in a 2-day integral equation whichwas precisely and rapidly solved via sinc-convolution algorithm to find the square root of theconductivity for each pixel of image. For the purpose of comparison, multigrid and NOSERalgorithms were implemented under a similar setting. Quality of reconstructions of syntheticmodels was tested against GREIT approved quality measures. To validate the simulationresults, reconstructions of a phantom chest and a human lung were used. RESULTS: Evaluation of synthetic reconstructions shows that the quality of sinc-convolutionreconstructions is considerably better than that of each of its competitors in terms ofamplitude response, position error, ringing, resolution and shape-deformation. In addition, theresults confirm near-exponential and linear convergence rates for sinc-convolution andmultigrid, respectively. Moreover, the least degree of relative errors and the most degree oftruth were found in sinc-convolution reconstructions from experimental phantom data.Reconstructions of clinical lung data show that the related physiological effect is wellrecovered by sinc-convolution algorithm. CONCLUSIONS: Parametric evaluation demonstrates the efficiency of sinc-convolution to reconstruct accurateconductivity images from experimental data. Excellent results in phantom and clinicalreconstructions using sinc-convolution support parametric assessment results and suggest thesinc-convolution to be used for precise clinical EIT applications. 相似文献