全文获取类型
收费全文 | 698篇 |
免费 | 25篇 |
国内免费 | 2篇 |
专业分类
725篇 |
出版年
2023年 | 9篇 |
2022年 | 17篇 |
2021年 | 39篇 |
2020年 | 19篇 |
2019年 | 13篇 |
2018年 | 31篇 |
2017年 | 19篇 |
2016年 | 16篇 |
2015年 | 22篇 |
2014年 | 38篇 |
2013年 | 48篇 |
2012年 | 51篇 |
2011年 | 30篇 |
2010年 | 33篇 |
2009年 | 34篇 |
2008年 | 22篇 |
2007年 | 18篇 |
2006年 | 18篇 |
2005年 | 18篇 |
2004年 | 18篇 |
2003年 | 14篇 |
2002年 | 9篇 |
2001年 | 15篇 |
2000年 | 7篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 9篇 |
1990年 | 9篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 3篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1975年 | 7篇 |
1974年 | 5篇 |
1973年 | 2篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1966年 | 3篇 |
排序方式: 共有725条查询结果,搜索用时 15 毫秒
101.
Deepa Geeta Devi Yadav Pooja Chaudhary Mohd Jubair Aalam Dhan Raj Meena Surendra Singh 《Chirality》2020,32(1):64-72
Imidazolidin-4-one is used as a recoverable organocatalyst for the asymmetric Diels-Alder reaction in the presence of catalytic amount of dicationic ionic liquid and trifluoroacetic acid as a co-catalyst. The Diels-Alder reaction between model substrate cyclopentadiene and crotonaldehyde gave the product in 95% conversion and 87% ee of the endo-product. The catalyst was shown better reusability when the 20 mol% of dicationic ionic liquid was used and catalyst was reused upto 5 cycles, conversion remains upto 3 recycles but ee of endo- 9 was slightly droped. 相似文献
102.
Monika Chaudhary Neeraj Kumar Ashish Baldi Ramesh Chandra M. Arockia Babu 《Journal of biomolecular structure & dynamics》2020,38(1):200-218
AbstractWith an endeavor to develop novel curcumin analogs as potential anti-cancer agents, we designed and synthesized a series of Knoevenagel condensates by clubbing pyrazole carbaldehydes at the active methylene carbon atom of the curcumin backbone. Molecular docking studies were carried out to target the proposed derivatives on human kinase β (IKKβ), a potential anti-cancer target. The chloro derivative displayed five hydrogen bond interactions with a docking score of ?11.874?kcal/mol higher than curcumin (docking score =??7.434?kcal/mol). This was supported by the fact that the propellant shaped derivatives fitted aptly into the binding pocket. Molecular simulations studies were also conducted on the lead molecule and the results figured out that the stable complexes were developed as the minimal deviations per residue of protein within the range of 0.11–0.92 Å. The screened compounds were synthesized, characterized and evaluated in vitro for cytotoxicity against cervical cancer cell line, HeLa using standard cell proliferation assay. Chloro derivative and bromo analog demonstrated IC50 (half maximal inhibitory concentration) value of 14.2 and 18.6 µg/ml, respectively, significantly lower than 42.4 µg/ml of curcumin and higher than 0.008 µg/ml of paclitaxel. Induction of apoptosis was evaluated in the terms of cleavage of caspase-3 enzyme and they also exhibited 69.6 and 65.4% of apoptosis significantly higher than 19.9% induced by curcumin. In conclusion, chloro and bromo derivatives must be evaluated under a set of stringent in vitro and in vivo parameters for translating in to a clinically viable product.Communicated by Ramaswamy H. Sarma 相似文献
103.
104.
Ian Tagge Audrey O’Connor Priya Chaudhary Jim Pollaro Yosef Berlow Megan Chalupsky Dennis Bourdette Randy Woltjer Mac Johnson William Rooney 《PloS one》2016,11(4)
Cuprizone administration in mice provides a reproducible model of demyelination and spontaneous remyelination, and has been useful in understanding important aspects of human disease, including multiple sclerosis. In this study, we apply high spatial resolution quantitative MRI techniques to establish the spatio-temporal patterns of acute demyelination in C57BL/6 mice after 6 weeks of cuprizone administration, and subsequent remyelination after 6 weeks of post-cuprizone recovery. MRI measurements were complemented with Black Gold II stain for myelin and immunohistochemical stains for associated tissue changes. Gene expression was evaluated using the Allen Gene Expression Atlas. Twenty-five C57BL/6 male mice were split into control and cuprizone groups; MRI data were obtained at baseline, after 6 weeks of cuprizone, and 6 weeks post-cuprizone. High-resolution (100μm isotropic) whole-brain coverage magnetization transfer ratio (MTR) parametric maps demonstrated concurrent caudal-to-rostral and medial-to-lateral gradients of MTR decrease within corpus callosum (CC) that correlated well with demyelination assessed histologically. Our results show that demyelination was not limited to the midsagittal line of the corpus callosum, and also that opposing gradients of demyelination occur in the lateral and medial CC. T2-weighted MRI gray/white matter contrast was strong at baseline, weak after 6 weeks of cuprizone treatment, and returned to a limited extent after recovery. MTR decreases during demyelination were observed throughout the brain, most clearly in callosal white matter. Myelin damage and repair appear to be influenced by proximity to oligodendrocyte progenitor cell populations and exhibit an inverse correlation with myelin basic protein gene expression. These findings suggest that susceptibility to injury and ability to repair vary across the brain, and whole-brain analysis is necessary to accurately characterize this model. Whole-brain parametric mapping across time is essential for gaining a real understanding of disease processes in-vivo. MTR increases in healthy mice throughout adolescence and adulthood were observed, illustrating the need for appropriate age-matched controls. Elucidating the unique and site-specific demyelination in the cuprizone model may offer new insights into in mechanisms of both damage and repair in human demyelinating diseases. 相似文献
105.
106.
107.
Chuansheng Niu Diane H. Boschelli L. Nathan Tumey Niala Bhagirath Joan Subrath Jaechul Shim Yan Wang Biqi Wu Clark Eid Julie Lee Xiaoke Yang Agnes Brennan Divya Chaudhary 《Bioorganic & medicinal chemistry letters》2009,19(20):5829-5832
A series of 5-vinyl-3-pyridinecarbonitriles were synthesized and evaluated as PKCθ inhibitors. The systematic optimization of 4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-phenylvinyl]-3-pyridinecarbonitrile 3 resulted in the identification of compound 23e as a potent PKCθ inhibitor with good selectivity over PKCδ. 相似文献
108.
Short peptides have been identified from amyloidogenic proteins that form amyloid fibrils in isolation. The hexapeptide stretch
21DIDLHL26 has been shown to be important in the self-assembly of the Src homology 3 (SH3) domain of p85α subunit of bovine phosphatidylinositol-3-kinase
(PI3-SH3). The SH3 domain of chicken brain α-spectrin, which is otherwise non-amyloidogenic, is rendered amyloidogenic if
22EVTMKK27 is replaced by DIDLHL. In this article, we describe the aggregation behaviour of DIDLHL-COOH and DIDLHL-CONH2. Our results indicate that DIDLHL-COOH and DIDLHL-CONH2 aggregate to form spherical structures at pH 5 and 6. At pH 5, in the presence of mica, DIDLHL-CONH2 forms short fibrous structures. The presence of NaCl along with mica results in fibrillar structures. At pH 6, DIDLHL-CONH2 forms largely spherical aggregates. Both the peptides are unstructured in solution but adopt β-conformation on drying. The
aggregates formed by DIDLHL-COOH and DIDLHL-CONH2 are formed during drying process and their structures are modulated by the presence of mica and salt. Our study suggests
that a peptide need not have intrinsic amyloidogenic propensity to facilitate the self-assembly of the full-length protein.
The propensity of peptides to form self-assembled structures that are non-amyloidogenic could be important in potentiating
the self-assembly of full-length proteins into amyloid fibrils. 相似文献
109.
Species of the monogenean genus Thaparocleidus are specific to freshwater siluriform fish. The infection caused by these gill
parasites are a major health problem to fish. But, to focus the control strategies of these parasites, first it is important to establish an
accurate discrimination by molecular methods. In the present study, phylogenetic and structural analysis of 28S region of
ribosomal DNA of T. wallagonius species collected from fish Wallago attu from Meerut (U.P.), India, was carried out. In the first step,
we amplified, sequenced 28S region of ribosomal DNA of T. wallagonius to establish the phylogenetic relationship with other
species of this genus. T. wallagonius found on gill filaments of fish W. attu, is the most primitive parasite of this genus from India,
was unequivocally discriminate from other species of the same genus in this study. A secondary-structure model of the large
subunit rDNA was also predicted using a combined comparative and thermodynamic approach. Molecular morphometric and
phylogenetic relationship of T. wallagonius are discussed in detailed that based on molecular analysis using bioinformatic tools. 相似文献
110.
Chawla R Arora R Kumar R Sharma A Prasad J Singh S Sagar R Chaudhary P Shukla S Kaur G Sharma RK Puri SC Dhar KL Handa G Gupta VK Qazi GN 《Molecular and cellular biochemistry》2005,273(1-2):193-208
Whole extract of rhizomes of Podophyllum hexandrum has been reported earlier by our group to render whole-body radioprotection. High-altitude P. hexandrum (HAPH) was therefore fractionated using solvents of varying polarity (non-polar to polar) and the different fractions were designated as, n-hexane (HE), chloroform (CE), alcohol (AE), hydro-alcohol (HA) and water (WE). The total polyphenolic content (mg% of quercetin) was determined spectrophotometrically, while. The major constituents present in each fraction were identified and characterized using LC-APCI/MS/MS. In vitro screening of the individual fractions, rich in polyphenols and lignans, revealed several bioactivities of direct relevance to radioprotection e.g. metal-chelation activity, antioxidant activity, DNA protection, inhibition of radiation (250 Gy) and iron/ascorbate-induced lipid peroxidation (LPO). CE exhibited maximum protection to plasmid (pBR322) DNA in the plasmid relaxation assay (68.09% of SC form retention). It also showed maximal metal chelation activity (41.59%), evaluated using 2,2-bipyridyl assay, followed by AE (31.25%), which exhibited maximum antioxidant potential (lowest absorption unit value: 0.0389± 0.00717) in the reducing power assay. AE also maximally inhibited iron/ascorbate-induced and radiation-induced LPO (99.76 and 92.249%, respectively, at 2000 g/ml) in mouse liver homogenate. Under conditions of combined stress (radiation (250 Gy) + iron/ascorbate), at a concentration of 2000 g/ml, HA exhibited higher percentage of inhibition (93.05%) of LPO activity. HA was found to be effective in significantly (p < 0.05) lowering LPO activity over a wide range of concentrations as compared to AE. The present comparative study indicated that alcoholic (AE) and hydro-alcoholic (HA) fractions are the most promising fractions, which can effectively tackle radiation-induced oxidative stress. 相似文献