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231.
Protein denaturations encountered during the different types of chromatographic separations are presented. The analysis of different protein denaturations presented along with the causes of such denaturations provides a judicious framework to compare protein denaturations encountered by such separation techniques. Especially of interest are those studies which compare the mass recovery of proteins and the retention of activity by different chromatographic techniques. Reversed-phase chromatography is presented even though it is utilized nowadays only for specialized cases such as separation of small peptides. It appears that relatively mild interactions that are encountered generally in hydrocarbon-interaction chromatography are favorable to the preservation of the native (active) protein state. The few available mechanistic studies presented provide judicious physical insights into protein conformational behavior on chromatographic columns. 相似文献
232.
M R Raju M Gnanapurani B Stackler B I Martins U Madhvanath J Howard J T Lyman R K Mortimer 《Radiation research》1971,47(3):635-643
233.
High resolution nuclear magnetic resonance spectra of native or protease-treated hen’s egg yolk plasma (very low density lipoproteins)
were taken either in water or deuterated water; the protease-treated samples showed a sharpening of choline methyl proton
signal of phospholipid, indicating the hindrance of the choline head-group rotation by the phospholipids in the native very
low density lipoproteins. With both native and the protease-treated egg yolk plasma, elevated temperatue increased the signal
intensity and produced line-sharpening of Q choline methyl protons and the — CH2-C-protons of the methylene group adjacent to the carboxyl group of esterified fatty acids, indicating prior restriction of
mobility of these groups. Total extracted lipids of egg yolk plasma containing traces of chloroform, methanol and water (which
keep the sample in one phase) also gave similar temperature dependence. Addition of water to the same sample and sonication
resulted in the loss of temperature dependence. Frozen and thawed protease-treated egg yolk plasma also behaved in a similar
manner. The absence of temperature dependence in these latter two samples is believed to be due to formation of bilayers of
phospholipids following phase separation of triglycerides and phospholipids. The results support a model in which the lipoprotein
particles of the egg yolk plasma have a lipid-core structure containing triglycerides in the centre with a monomolecular layer
of lecithin at the surface, the polar heads of which are surrounded by proteins.
Contribution No. 149 from the Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012. 相似文献
234.
Alan K. Hunter Kamiyar Rezvani Matthew T. Aspelund Guoling Xi Dhanesh Gadre Thomas Linke Kang Cai Sri Hari Raju Mulagapati Tomasz Witkos 《Biotechnology progress》2022,38(2):e3235
We have systematically investigated six compendial nonionic detergents as potential replacements for Triton ×-100 in bioprocessing applications. Use of compendial raw materials in cGMP bioprocessing is advantageous for a variety of reasons including material specifications developed to meet stringent pharmaceutical product quality requirements, regulatory familiarity and comfort, and availability from vendors experienced supplying the biopharmaceutical industry. We first examine material properties of the detergents themselves including melting point and viscosity. Process performance and product contact in real-world bioprocess applications are then investigated. Lastly, we test the detergents in virus inactivation (VI) experiments with recombinant proteins and adeno-associated virus. Two of the detergents tested, PEG 9 Lauryl Ether and PEG 6 Caprylic/Capric Glycerides, showed favorable properties that make them attractive for use as potential Triton X-100 replacements. Process performance testing indicated negligible impact of the detergents on product yield, purity, and activity compared to a control with no detergent. Importantly, both PEG 9 Lauryl Ether and PEG 6 Caprylic/Capric Glycerides demonstrated very fast VI kinetics with complete inactivation of XMuLV observed in less than 1 min at a target 1% detergent concentration. Potential advantages and disadvantages of both candidate detergents for use in cGMP bioprocessing are summarized and discussed. 相似文献
235.
Julien Prunier Isabelle Gigure Natalie Ryan Robert Guy Raju Soolanayakanahally Nathalie Isabel John MacKay Ilga Porth 《Molecular ecology》2019,28(6):1476-1490
Gene copy number variations (CNVs) involved in phenotypic variations have already been shown in plants, but genomewide testing of CNVs for adaptive variation was not doable until recent technological developments. Thus, reports of the genomic architecture of adaptation involving CNVs remain scarce to date. Here, we investigated F1 progenies of an intraprovenance cross (north–north cross, 58th parallel) and an interprovenances cross (north–south cross, 58th/49th parallels) for CNVs using comparative genomic hybridization on arrays of probes targeting gene sequences in balsam poplar (Populus balsamifera L.), a widespread North American forest tree. A total of 1,721 genes were found in varying copy numbers over the set of 19,823 tested genes. These gene CNVs presented an estimated average size of 8.3 kb and were distributed over poplar's 19 chromosomes including 22 hotspot regions. Gene CNVs number was higher for the interprovenance progeny in accordance with an expected higher genetic diversity related to the composite origin of this family. Regression analyses between gene CNVs and seven adaptive trait variations resulted in 23 significant links; among these adaptive gene CNVs, 30% were located in hotspots. One‐to‐five gene CNVs were found related to each of the measured adaptive traits and annotated for both biotic and abiotic stress responses. These annotations can be related to the occurrence of a higher pathogenic pressure in the southern parts of balsam poplar's distribution, and higher photosynthetic assimilation rates and water‐use efficiency at high latitudes. Overall, our findings suggest that gene CNVs typically having higher mutation rates than SNPs may in fact represent efficient adaptive variations against fast‐evolving pathogens. 相似文献
236.
Kumar Subramani Xiaogang Chu Marie Warren Mariah Lee Sumin Lu Nagendra Singh Raghavan Raju 《生物化学与生物物理学报:疾病的分子基础》2019,1865(3):688-695
Inflammation and cellular energetics play critical roles in organ dysfunction following hemorrhagic shock. Recent studies suggest a putative role for sirtuin 1 (SIRT1) in potentiating mitochondrial function and improving organ function following hemorrhagic shock in animal models. SIRT1 is an NAD+ dependent protein deacetylase and increased availability of NAD+ has been shown to augment SIRT1 activity. As niacin is a precursor of NAD+, in this study, we tested whether niacin can improve survival following hemorrhagic shock. However niacin also mediates its biological action by binding to its receptor, hydroxyl-carboxylic acid receptor 2 (HCA2 or Gpr109a); so we examined whether the effect of niacin is mediated by binding to Gpr109a or by increasing NAD+ availability. We found that niacin administered intravenously to rats subjected to hemorrhagic injury (HI) in the absence of fluid resuscitation resulted in a significantly prolonged duration of survival. However, treatment of rats with similar doses of nicotinamide mononucleotide (NMN), a precursor to NAD+ that does not bind Gpr109a, did not extend survival following HI. The duration of survival due to niacin treatment was significantly reduced in Gpr109a?/? mice subjected to HI. These experiments demonstrated that the Gpr109a receptor-mediated pathway contributed significantly to niacin mediated salutary effect. Further studies showed improvement in markers of cellular energetics and attenuation of inflammatory response with niacin treatment. In conclusion, we report that Gpr109a-dependent signalling is important in restoring cellular energetics and immunometabolism following hemorrhagic shock. 相似文献
237.
Benzimidazole tethered pyrrolo[3,4-b]quinoline with broad-spectrum activity against fungal pathogens
Pedro Villa Natarajan Arumugam Abdulrahman I. Almansour Raju Suresh Kumar S.M. Mahalingam Keiji Maruoka Shankar Thangamani 《Bioorganic & medicinal chemistry letters》2019,29(5):729-733
Fungal infections caused by Candida and Cryptococcus are particularly dangerous for immunocompromised individuals. In this study, we identified that benzimidazole fused pyrrolo[3,4-b]quinoline compounds have potent antifungal activity against several clinical isolates of pathogenic fungal strains. Specifically, the compound 6a did not show cytotoxicity against mammalian cells at a concentration that inhibits the growth of fungal strains. In addition, the compound 6a also significantly reduced the metabolic activity of fungal cells in the Candida albicans biofilms. Collectively, our results indicate that benzimidazole fused quinoline compounds have a potential to develop as an antifungal agents. 相似文献
238.
239.
240.
Nesspor TC Raju TS Chin CN Vafa O Brezski RJ 《Journal of molecular recognition : JMR》2012,25(3):147-154
Immunoglobulin G (IgG) antibodies are an integral part of the adaptive immune response that provide a direct link between humoral and cellular components of the immune system. Insights into relationships between the structure and function of human IgGs have prompted molecular engineering efforts to enhance or eliminate specific properties, such as Fc-mediated immune effector functions. Human IgGs have an N-glycosylation site at Asn297, located in the second heavy chain constant region (CH2). The composition of the Fc glycan can have substantial impacts on Fc gamma receptor(FcγR) binding. The removal of the glycan through enzymatic deglycosylation or mutagenesis of the N-linked glycosylation site has been reported to "silence" FcγR-binding and effector functions, particularly with assays that measure monomeric binding. However, interactions between IgGs and FcγRs are not limited to monomeric interactions but can be influenced by avidity, which takes into account the sum of multimeric interactions between antigen-engaged IgGs and FcγRs. We show here that under in vitro conditions, which allowed avidity binding, aglycosylated IgGs can bind to one of the FcγRs, FcγRI, and mediate effector functions. These studies highlight how the valency of a molecular interaction (monomeric binding versus avidity binding) can influence antibody/FcγR interactions such that avidity effects can translate very low intrinsic affinities into significant functional outcomes. 相似文献