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71.
Bidya Dhar Sahu Anil Kumar Kalvala Meghana Koneru Jerald Mahesh Kumar Madhusudana Kuncha Shyam Sunder Rachamalla Ramakrishna Sistla 《PloS one》2014,9(9)
Nephrotoxicity is a dose-dependent side effect of cisplatin limiting its clinical usage in the field of cancer chemotherapy. Fisetin is a bioactive flavonoid with recognized antioxidant and anti-inflammatory properties. In the present study, we investigated the potential renoprotective effect and underlying mechanism of fisetin using rat model of cisplatin-induced nephrotoxicity. The elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine); degree of histopathological alterations and oxidative stress were significantly restored towards normal in fisetin treated, cisplatin challenged animals. Fisetin treatment also significantly attenuated the cisplatin-induced IκBα degradation and phosphorylation and blocked the NF-κB (p65) nuclear translocation, with subsequent elevation of pro-inflammatory cytokine, TNF-α, protein expression of iNOS and myeloperoxidase activities. Furthermore, fisetin markedly attenuated the translocation of cytochrome c protein from the mitochondria to the cytosol; decreased the expression of pro-apoptotic proteins including Bax, cleaved caspase-3, cleaved caspase-9 and p53; and prevented the decline of anti-apoptotic protein, Bcl-2. The cisplatin-induced mRNA expression of NOX2/gp91phox and NOX4/RENOX and the NADPH oxidase enzyme activity were also significantly lowered by fisetin treatment. Moreover, the evaluated mitochondrial respiratory enzyme activities and mitochondrial antioxidants were restored by fisetin treatment. Estimation of platinum concentration in kidney tissues revealed that fisetin treatment along with cisplatin did not alter the cisplatin uptake in kidney tissues. In conclusion, these findings suggest that fisetin may be used as a promising adjunct candidate for cisplatin use. 相似文献
72.
Aishwarya Natarajan Krishnan Rangan Ramakrishna Vadrevu 《Journal of peptide science》2023,29(2):e3451
The self-assembly of peptides is influenced by their amino acid sequence and other factors including pH, charge, temperature, and solvent. Herein, we explore whether a four-residue sequence, EKKE, consisting of exclusively charged amino acids shows the propensity to form self-assembled ordered nanostructures and whether the overall charge plays any role in morphological and functional properties. From a combination of experimental data provided by Thioflavin T fluorescence, Congo red absorbance, circular dichroism spectroscopy, dynamic light scattering, field emission-scanning electron microscopy, atomic force microscopy, and confocal microscopy, it is clear that the all-polar peptide and charged EKKE sequence shows a pH-dependent tendency to form amyloid-like structures, and the self-assembled entities under acidic, basic and neutral conditions exhibit morphological variation. Additionally, the ability of the self-assembled amyloid nanostructures to bind to the toxic metal, lead (Pb2+), was demonstrated from the analysis of the ultraviolet absorbance and X-ray photoelectron spectroscopy data. The modulation at the sequence level for the amyloid-forming EKKE scaffold can further extend its potential role not only in the remediation of other toxic metals but also towards biomedical applications. 相似文献
73.
74.
Harikrishnan LS Kamau MG Herpin TF Morton GC Liu Y Cooper CB Salvati ME Qiao JX Wang TC Adam LP Taylor DS Chen AY Yin X Seethala R Peterson TL Nirschl DS Miller AV Weigelt CA Appiah KK O'Connell JC Michael Lawrence R 《Bioorganic & medicinal chemistry letters》2008,18(8):2640-2644
2-Arylbenzoxazole 5 was identified as a hit from a fluorescence-based high-throughput screen for CETP inhibitors. The synthesis and SAR investigation employing array synthesis of the A- and B-rings are described. 相似文献
75.
Li JJ Wang H Li J Qu F Swartz SG Hernández AS Biller SA Robl JA Tino JA Slusarchyk D Seethala R Sleph P Yan M Grover G Flynn N Murphy BJ Gordon D 《Bioorganic & medicinal chemistry letters》2008,18(8):2536-2539
A novel series of N1 substituted tetrazole amides were prepared and showed to be potent growth hormone (GH) secretagogues. Among them, hydroxyl containing analog 31 displayed excellent in vivo activity by increasing plasma GH 10-fold in an anesthetized IV rat model. 相似文献
76.
Critical leaf nutrient concentrations have often been used to diagnose the nutritional causes of crop underperformance. Unfortunately, these diagnostic criteria are not available for mature, tuber-bearing sweet potato plants (the word ‘tuber’ being used to describe a swollen root rather than a swollen stem). The Diagnosis and Recommendation Integrated System (DRIS), however, provides a reliable means of linking leaf nutrient concentrations to the yield of sweet potato tubers, and may be developed for this crop using existing data from regional crop surveys. In the present study, tuber yield and leaf nutrient concentration data from a survey of sweet potato gardens conducted in the Papua New Guinea (PNG) highlands in 2005 were used to establish DRIS N, P, K, and S norms and statistical parameters for sweet potato. Although the database was relatively small, the norms derived for nutrient ratios of key biological significance, i.e. N/S and K/N, were within the expected narrow ranges for higher plants, giving credibility to both the database and the DRIS model. Data from future surveys and field trials may subsequently be used to enlarge the database allowing the refinement of model parameters and hopefully an expansion of diagnostic scope to include other macro and micro-nutrients. As it stands, though, this preliminary DRIS model for sweet potato is possibly the best diagnostic tool currently available for evaluating the N, P, K and S statuses of sweet potato crops in the pacific region. 相似文献
77.
Dynein light chain (DLC8) is the smallest subunit of the dynein motor complex, which is known to act as a cargo adaptor in intracellular trafficking. The protein exists as a pure dimer at physiological pH and a completely folded monomer below pH 4. Here, we have determined the energy landscape of the dimeric protein using a combination of optical techniques and native-state hydrogen exchange of amide groups, the former giving the global features and the latter yielding the residue level details. The data indicated the presence of intermediates along the equilibrium unfolding transition. The hydrogen exchange data suggested that the molecule has differential stability in its various segments. We deduce from the free energy data that the antiparallel beta-sheets (beta4 and beta5) that form the hydrophobic core of the protein and the alpha2 helix, all of which are highly protected with regard to hydrogen exchange, contribute significantly to the initial step of the protein folding mechanism. Denaturant-dependent hydrogen exchange indicated further that some amides exchange via local fluctuations, whereas there are others which exchange via global unfolding events. Implications of these to cargo adaptability of the dimer are discussed. 相似文献
78.
Ch. Srinivas Ch.N.S. Sai Pavan Kumar B. China Raju V. Jayathirtha Rao V.G.M. Naidu S. Ramakrishna Prakash V. Diwan 《Bioorganic & medicinal chemistry letters》2009,19(20):5915-5918
The first stereoselective total synthesis of new natural amide alkaloids 1–3 have been achieved from commercially available starting materials. Wittig olefination, Sharpless asymmetric dihydroxylation, epoxidation, a trans regioselective opening of 2,3-epoxy alcohol, Horner–Wadsworth–Emmons (HWE) olefination and amide coupling are the key steps. The amide alkaloids 1–3 are evaluated for their anticancer activity against colon (HT-29), breast (MCF-7) and lung (A-549) human cancer cell lines for the first time. 相似文献
79.
Tasir S. Haque Ningning Liang Rajasree Golla Ramakrishna Seethala Zhengping Ma William R. Ewing Christopher B. Cooper Mary Ann Pelleymounter Michael A. Poss Dong Cheng 《Bioorganic & medicinal chemistry letters》2009,19(20):5872-5876
We report the synthesis and enzymatic evaluation of potent inhibitors of acetyl-CoA carboxylases (ACCs) containing biphenyl or 3-phenyl pyridine cores. These compounds inhibit both ACC1 and ACC2, or are moderately selective for either enzyme, depending on side chain substitution. Typical activities of the most potent compounds in this class are in the low double-digit to single-digit nanomolar range in in vitro assays using human ACC1 and ACC2 enzymes. 相似文献
80.
Gene order and content differ among homologous regions of closely related genomes. Similarities in the expression profiles of physically adjacent genes suggest that the proper functioning of these genes depends on maintaining a specific position relative to each other. To better understand the results of the interaction of these two genomic forces, convergent, divergent, and tandem gene pairs in rice and sorghum, as well as their homologs in rice, sorghum, maize, and Brachypodium were analyzed. The status of each pair in all four species: whether it was conserved, inverted, rearranged, or missing homologs was determined. We observed that divergent gene pairs had lower rates of conservation than convergent or tandem pairs, but higher rates of rearranged pairs and missing homologs in maize than in any other species. We also discovered species-specific gene pairs in rice and sorghum. In rice, gene pairs with strongly correlated expression levels were conserved significantly more often than those with little or no correlation. We assigned three types of gene pair to one of 14 possible evolutionary history categories to uncover their evolutionary dynamics during the evolution of grass genomes. 相似文献