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21.
Preeti Rajesh Changanamkandath Rajesh Michael D. Wyatt Douglas L. Pittman 《DNA Repair》2010,9(4):458-467
SN1-type methylating agents generate O6-methyl guanine (O6-meG), which is a potently mutagenic, toxic, and recombinogenic DNA adduct. Recognition of O6-meG:T mismatches by mismatch repair (MMR) causes sister chromatid exchanges, which are representative of homologous recombination (HR) events. Although the MMR-dependent mutagenicity and toxicity caused by O6-meG has been studied, the mechanisms of recombination induced by O6-meG are poorly understood. To explore the HR and MMR genetic interactions in mammals, we used the Rad51d and Mlh1 mouse models. Ablation of Mlh1 did not appreciably influence the developmental phenotypes conferred by the absence of Rad51d. Mouse embryonic fibroblasts (MEFs) deficient in Rad51d can only proliferate in p53-deficient background. Therefore, Rad51d?/?Mlh1?/? Trp53?/? MEFs with a combined deficiency of HR and MMR were generated and comparisons between MLH1 and RAD51D status were made. To our knowledge, these MEFs are the first mammalian model system for combined HR and MMR defects. Rad51d-deficient MEFs were 5.3-fold sensitive to N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) compared to the Rad51d-proficient MEFs. A pronounced G2/M arrest in Rad51d-deficient cells was accompanied by an accumulation of γ-H2AX and apoptosis. Mlh1-deficient MEFs were resistant to MNNG and showed no G2/M arrest or apoptosis at the doses used. Importantly, loss of Mlh1 alleviated sensitivity of Rad51d-deficient cells to MNNG, in addition to reducing γ-H2AX, G2/M arrest and apoptosis. Collectively, the data support the hypothesis that MMR-dependent sensitization of HR-deficient cells is specific for O6-meG and suggest that HR resolves DNA intermediates created by MMR recognition of O6-meG:T. This study provides insight into recombinogenic mechanisms of carcinogenesis and chemotherapy resulting from O6-meG adducts. 相似文献
22.
Sanjay Dwivedi R. D. Tripathi Sudhakar Srivastava Ragini Singh Amit Kumar Preeti Tripathi Richa Dave U. N. Rai Debasis Chakrabarty P. K. Trivedi R. Tuli B. Adhikari M. K. Bag 《Protoplasma》2010,245(1-4):113-124
The exposure of paddy fields to arsenic (As) through groundwater irrigation is a serious concern that may not only lead to As accumulation to unacceptable levels but also interfere with mineral nutrients in rice grains. In the present field study, profiling of the mineral nutrients (iron (Fe), phosphorous, zinc, and selenium (Se)) was done in various rice genotypes with respect to As accumulation. A significant genotypic variation was observed in elemental retention on root Fe plaque and their accumulation in various plant parts including grains, specific As uptake (29–167 mg kg?1 dw), as well as As transfer factor (4–45%). Grains retained the least level of As (0.7–3%) with inorganic As species being the dominant forms, while organic As species, viz., dimethylarsinic acid and monomethylarsonic acid, were non-detectable. In all tested varieties, the level of Se was low (0.05–0.12 mg kg?1 dw), whereas that of As was high (0.4–1.68 mg kg?1 dw), considering their safe/recommended daily intake limits, which may not warrant their human consumption. Hence, their utilization may increase the risk of arsenicosis, when grown in As-contaminated areas. 相似文献
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Mishra JK Garg P Dohare P Kumar A Siddiqi MI Ray M Panda G 《Bioorganic & medicinal chemistry letters》2007,17(5):1326-1331
A series of 3-substituted 1,4-benzodiazepin-2-ones derived from S and R amino acids were evaluated for their anti-ischemic activity in vitro. Treatment with compounds 7h, 16, 9d, and 17 decreased the apoptotic neuronal number, however increased the neuronal viability. The compounds decreasing apoptosis could protect neurons from the ischemic injury. The difference in the activities of 1,4-benzodiazepin-2-ones derived from S- and R-amino acids is discussed and explained on the basis of molecular modeling studies. 相似文献
25.
Renal clearance of quantum dots 总被引:9,自引:0,他引:9
Choi HS Liu W Misra P Tanaka E Zimmer JP Itty Ipe B Bawendi MG Frangioni JV 《Nature biotechnology》2007,25(10):1165-1170
The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using intravenously administered quantum dots in rodents as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter by >15 nm and prevented renal excretion. A final hydrodynamic diameter <5.5 nm resulted in rapid and efficient urinary excretion and elimination of quantum dots from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications. 相似文献
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Patidar Preeti Bhayal Mamta Hajela Sumati Hajela Krishnan 《Journal of plant biochemistry and biotechnology.》2022,31(4):961-964
Journal of Plant Biochemistry and Biotechnology - A glycosylated heat stable trypsin chymotrypsin inhibitor was isolated from Cyamopsis tetragonoloba seeds. It is being reported for the first time... 相似文献
28.
Kumar M Rawat P Khan MF Rawat AK Srivastava AK Maurya R 《Bioorganic & medicinal chemistry letters》2011,21(8):2232-2237
16-Dehydropregnenolone undergoes a smooth annulation with propan-1-amine and aromatic aldehydes. Several amine derivatives of 16- dehydropregnenolone were synthesized and evaluated as inhibitors of DPP-IV. The structures of compounds were confirmed by 1H, 13C, NMR and mass spectral analysis. Among 17 compounds evaluated only five compounds 1, 9, 13, 15 and 16 demonstrated significant inhibition of DPP. This study suggest that introduction of appropriate substituents in the 16-dehydropregnenolone plays an important role in DPP-IV inhibitory activity. 相似文献
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Sukerkar PA MacRenaris KW Townsend TR Ahmed RA Burdette JE Meade TJ 《Bioconjugate chemistry》2011,22(11):2304-2316
Progesterone receptor (PR) is strongly associated with disease prognosis and therapeutic efficacy in hormone-related diseases such as endometriosis and breast, ovarian, and uterine cancers. Receptor status is currently determined by immunohistochemistry assays. However, noninvasive PR imaging agents could improve disease detection and help elucidate pathological molecular pathways, leading to new therapies and animal disease models. A series of water-soluble PR-targeted magnetic resonance imaging (MRI) probes were synthesized using Cu(I)-catalyzed click chemistry and evaluated in vitro and in vivo. These agents demonstrated activation of PR in vitro and preferential accumulation in PR(+) compared to PR(-) human breast cancer cells with low toxicity. In xenograft tumor models, the agents demonstrated enhanced signal intensity in PR(+) tumors compared to PR(-) tumors. The results suggest that these agents may be promising MRI probes for PR(+) diseases. 相似文献