全文获取类型
收费全文 | 1726篇 |
免费 | 103篇 |
国内免费 | 1篇 |
出版年
2023年 | 4篇 |
2022年 | 25篇 |
2021年 | 43篇 |
2020年 | 32篇 |
2019年 | 34篇 |
2018年 | 61篇 |
2017年 | 39篇 |
2016年 | 62篇 |
2015年 | 78篇 |
2014年 | 97篇 |
2013年 | 124篇 |
2012年 | 139篇 |
2011年 | 138篇 |
2010年 | 80篇 |
2009年 | 65篇 |
2008年 | 105篇 |
2007年 | 101篇 |
2006年 | 92篇 |
2005年 | 75篇 |
2004年 | 78篇 |
2003年 | 63篇 |
2002年 | 67篇 |
2001年 | 21篇 |
2000年 | 15篇 |
1999年 | 15篇 |
1998年 | 24篇 |
1996年 | 14篇 |
1995年 | 7篇 |
1994年 | 9篇 |
1993年 | 6篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 8篇 |
1989年 | 7篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1969年 | 2篇 |
1961年 | 2篇 |
1960年 | 3篇 |
1959年 | 4篇 |
1958年 | 2篇 |
1957年 | 7篇 |
排序方式: 共有1830条查询结果,搜索用时 15 毫秒
141.
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
142.
Gaertner HF Cerini F Kamath A Rochat AF Siegrist CA Menin L Hartley O 《Bioconjugate chemistry》2011,22(6):1103-1114
Nanoparticles carrying biologically active functional sets (e.g., targeting moiety, payload, tracer) have potential use in a wide range of clinical applications. Though complex, such constructions should, as far as possible, have a defined molecular architecture and be monodisperse. However, the existing methods to achieve this goal are unsuitable for the incorporation of peptides and proteins, and those that provide for orthogonal introduction of two different types of functional element are incompatible with the use of commercially available materials. In this study, we have developed approaches for the production of nanoparticles based on commercially available polyamidoamine (PAMAM) dendrimers. First, we identified an optimized oxime conjugation strategy under which complex dendrimers can be fully decorated not only with model peptides, but also with recombinant proteins (insulin was taken as an example). Second, we developed a strategy based on a two-chain covalent heterodendrimer (a "diblock") based on cystamine core PAMAM dendrimers and used it to generate heterodendrimers, into which a peptide array and a mannose array were orthogonally introduced. Finally, by incorporating a functionalized linker into the diblock architecture we were able to site-specifically introduce a third functional element into the nanoparticle. We exemplified this approach using fluorescein, a mannose array, and a peptide array as the three functionalities. We showed that incorporation of a mannose array into a nanoparticle strongly and specifically enhances uptake by sentinel cells of the immune system, an important property for vaccine delivery applications. These PAMAM dendrimer-based approaches represent a robust and versatile platform for the development of bioactive nanoparticles. 相似文献
143.
Cho HY Srinivasan A Hong J Hsu E Liu S Shrivats A Kwak D Bohaty AK Paik HJ Hollinger JO Matyjaszewski K 《Biomacromolecules》2011,12(10):3478-3486
Star polymers with poly(ethylene glycol) (PEG) arms and a degradable cationic core were synthesized by the atom transfer radical copolymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate macromonomer (PEGMA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), and a disulfide dimethacrylate (cross-linker, SS) via an "arm-first" approach. The star polymers had a diameter ~15 nm and were degraded under redox conditions by glutathione treatment into individual polymeric chains due to cleavage of the disulfide cross-linker, as confirmed by dynamic light scattering. The star polymers were cultured with mouse calvarial preosteoblast-like cells, embryonic day 1, subclone 4 (MC3T3-E1.4) to determine biocompatibility. Data suggest star polymers were biocompatible, with ≥ 80% cell viability after 48 h of incubation even at high concentration (800 μg/mL). Zeta potential values varied with N/P ratio confirming complexation with siRNA. Successful cellular uptake of the star polymers in MC3T3-E1.4 cells was observed by confocal microscopy and flow cytometry after 24 h of incubation. 相似文献
144.
Azad A Jackson S Cullinane C Natoli A Neilsen PM Callen DF Maira SM Hackl W McArthur GA Solomon B 《Molecular cancer research : MCR》2011,9(12):1696-1707
DNA-dependent protein kinase (DNA-PK) plays a pivotal role in the repair of DNA double-strand breaks (DSB) and is centrally involved in regulating cellular radiosensitivity. Here, we identify DNA-PK as a key therapeutic target for augmenting accelerated senescence in irradiated human cancer cells. We find that BEZ235, a novel inhibitor of DNA-PK and phosphoinositide 3-kinase (PI3K)/mTOR, abrogates radiation-induced DSB repair resulting in cellular radiosensitization and growth delay of irradiated tumor xenografts. Importantly, radiation enhancement by BEZ235 coincides with a prominent p53-dependent accelerated senescence phenotype characterized by positive β-galactosidase staining, G(2)-M cell-cycle arrest, enlarged and flattened cellular morphology, and increased p21 expression and senescence-associated cytokine secretion. Because this senescence response to BEZ235 is accompanied by unrepaired DNA DSBs, we examined whether selective targeting of DNA-PK also induces accelerated senescence in irradiated cells. Significantly, we show that specific pharmacologic inhibition of DNA-PK, but not PI3K or mTORC1, delays DSB repair leading to accelerated senescence after radiation. We additionally show that PRKDC knockdown using siRNA promotes a striking accelerated senescence phenotype in irradiated cells comparable with that of BEZ235. Thus, in the context of radiation treatment, our data indicate that inhibition of DNA-PK is sufficient for the induction of accelerated senescence. These results validate DNA-PK as an important therapeutic target in irradiated cancer cells and establish accelerated senescence as a novel mechanism of radiosensitization induced by DNA-PK blockade. 相似文献
145.
B.S. Ashok Kumar K. Lakshman R. Nandeesh P.A. Arun Kumar B. Manoj Vinod Kumar D. Sheshadri Shekar 《Saudi Journal of Biological Sciences》2011,18(1):1-5
Amaranthus spinosus Linn. (Amaranthaceae), commonly known as “Mulluharivesoppu” in Kannada, is used in the Indian traditional system of medicine for the treatment of diabetes. The present study deals with the scientific evaluation of alpha amylase and the antioxidant potential of methanol extract of A. spinosus (MEAS). The aim of this study was to investigate in vitro alpha-amylase enzyme inhibition by CNPG3 (2-chloro-4-nitrophenol α-d-maltotrioside) and in vivo antioxidant potential of malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and total thiols (TT) in alloxan-induced diabetic rats of a methanolic extract of A. spinosus. Blood sugar was also determined in MEAS-treated alloxan-induced diabetic rats. MEAS showed significant inhibition of alpha-amylase activity and IC50 46.02 μg/ml. Oral administration of MEAS (200 and 400 mg/kg) for 15 days showed significant reduction in the elevated blood glucose, MDA and restores GSH, CAT and TT levels as compared with a diabetic control. The present study provides evidence that the methanolic extract of A. spinosus has potent alpha amylase, anti-diabetic and antioxidant activities. 相似文献
146.
Arockiaraj J Vanaraja P Easwvaran S Singh A Othman RY Bhassu S 《Fish & shellfish immunology》2011,31(6):1259-1267
147.
148.
149.
Senescence marker protein 30 (SMP30) expression in eukaryotic cells: existence of multiple species and membrane localization 总被引:1,自引:0,他引:1
Senescence marker protein (SMP30), also known as regucalcin, is a 34 kDa cytosolic marker protein of aging which plays an important role in intracellular Ca(2+) homeostasis, ascorbic acid biosynthesis, oxidative stress, and detoxification of chemical warfare nerve agents. In our goal to investigate the activity of SMP30 for the detoxification of nerve agents, we have produced a recombinant adenovirus expressing human SMP30 as a fusion protein with a hemaglutinin tag (Ad-SMP30-HA). Ad-SMP30-HA transduced the expression of SMP30-HA and two additional forms of SMP30 with molecular sizes ~28 kDa and 24 kDa in HEK-293A and C3A liver cells in a dose and time-dependent manner. Intravenous administration of Ad-SMP30-HA in mice results in the expression of all the three forms of SMP30 in the liver and diaphragm. LC-MS/MS results confirmed that the lower molecular weight 28 kDa and 24 kDa proteins are related to the 34 kDa SMP30. The 28 kDa and 24 kDa SMP30 forms were also detected in normal rat liver and mice injected with Ad-SMP30-HA suggesting that SMP30 does exist in multiple forms under physiological conditions. Time course experiments in both cell lines suggest that the 28 kDa and 24 kDa SMP30 forms are likely generated from the 34 kDa SMP30. Interestingly, the 28 kDa and 24 kDa SMP30 forms appeared initially in the cytosol and shifted to the particulate fraction. Studies using small molecule inhibitors of proteolytic pathways revealed the potential involvement of β and γ-secretases but not calpains, lysosomal proteases, proteasome and caspases. This is the first report describing the existence of multiple forms of SMP30, their preferential distribution to membranes and their generation through proteolysis possibly mediated by secretase enzymes. 相似文献
150.
Arun Kumar Tripathi Rajendra Singh Bhakuni Shikha Upadhyay Rashmi Gaur 《Insect Science》2011,18(2):189-194
Abstract Artemisia annua (Asteraceae) is well known for its antimalarial activities due to presence of the compound artemisinin. We isolated a methoxy coumarin from the stem part of A. annua and confirmed its identity as scopoletin through mass spectral data. The structure was established from 1H‐nuclear magnetic resonance (NMR), 13C‐NMR. The compound scopoletin was evaluated for its feeding deterrence and growth inhibitory potential against a noxious lepidopteran insect, Spilartctia obliqua Walker. Scopoletin gave FD50 (feeding deterrence of 50%) value of 96.7 μg/g diet when mixed into artificial diet. S. obliqua larvae (12‐day‐old) exposed to the highest concentration (250 μg/g diet) of scopoletin showed 77.1% feeding‐deterrence. In a growth inhibitory assay, scopoletin provided 116.9% growth inhibition at the highest dose of 250 μg/g diet with a GI50 (growth inhibition of 50%) value of 20.9 μg/g diet. Statistical analysis showed a concentration‐dependent dose response relationship toward both feeding deterrent and growth inhibitory activities. Artemisinin is found mainly in the leaves of A. annua and not in the stems, which are typically discarded as waste. Therefore identification of scopoletin in stems of A. annua may be important as a source of this material for pest control. 相似文献