全文获取类型
收费全文 | 2322篇 |
免费 | 200篇 |
国内免费 | 55篇 |
出版年
2024年 | 5篇 |
2023年 | 36篇 |
2022年 | 33篇 |
2021年 | 125篇 |
2020年 | 77篇 |
2019年 | 80篇 |
2018年 | 89篇 |
2017年 | 55篇 |
2016年 | 95篇 |
2015年 | 154篇 |
2014年 | 151篇 |
2013年 | 172篇 |
2012年 | 205篇 |
2011年 | 213篇 |
2010年 | 107篇 |
2009年 | 90篇 |
2008年 | 126篇 |
2007年 | 100篇 |
2006年 | 82篇 |
2005年 | 86篇 |
2004年 | 63篇 |
2003年 | 58篇 |
2002年 | 48篇 |
2001年 | 25篇 |
2000年 | 32篇 |
1999年 | 34篇 |
1998年 | 13篇 |
1997年 | 15篇 |
1996年 | 23篇 |
1995年 | 9篇 |
1994年 | 15篇 |
1993年 | 7篇 |
1992年 | 19篇 |
1991年 | 11篇 |
1990年 | 17篇 |
1989年 | 15篇 |
1988年 | 15篇 |
1987年 | 4篇 |
1986年 | 9篇 |
1985年 | 10篇 |
1984年 | 11篇 |
1983年 | 9篇 |
1982年 | 3篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1971年 | 2篇 |
1969年 | 2篇 |
排序方式: 共有2577条查询结果,搜索用时 125 毫秒
991.
Kareem L. Graham Jian V. Zhang Susanna Lewén Thomas M. Burke Ton Dang Maria Zoudilova Raymond A. Sobel Eugene C. Butcher Brian A. Zabel 《PloS one》2014,9(12)
Therapies that target leukocyte trafficking pathways can reduce disease activity and improve clinical outcomes in multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) is a widely studied animal model that shares many clinical and histological features with MS. Chemokine-like receptor-1 (CMKLR1) is a chemoattractant receptor that is expressed by key effector cells in EAE and MS, including macrophages, subsets of dendritic cells, natural killer cells and microglia. We previously showed that CMKLR1-deficient (CMKLR1 KO) mice develop less severe clinical and histological EAE than wild-type mice. In this study, we sought to identify CMKLR1 inhibitors that would pharmaceutically recapitulate the CMKLR1 KO phenotype in EAE. We identified 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA) as a CMKLR1 small molecule antagonist that inhibits chemerin-stimulated β-arrestin2 association with CMKLR1, as well as chemerin-triggered CMKLR1+ cell migration. α-NETA significantly delayed the onset of EAE induced in C57BL/6 mice by both active immunization with myelin oligodendrocyte glycoprotein peptide 35-55 and by adoptive transfer of encephalitogenic T cells. In addition, α-NETA treatment significantly reduced mononuclear cell infiltrates within the CNS. This study provides additional proof-of-concept data that targeting CMKLR1:chemerin interactions may be beneficial in preventing or treating MS. 相似文献
992.
The xylan-binding module Clostridium thermocellum CBM22A was successfully fused to a gluco-oligosaccharide oxidase, GOOX-VN, from Sarocladium strictum via a short TP linker, allowing the fused protein to effectively bind different xylans. The presence of the CtCBM22A at the N-terminal of GOOX-VN increased catalytic activity on mono- and oligo-saccharides by 2-3 fold while not affecting binding affinity to these substrates. Notably, both GOOX-VN and its CBM fusion also showed oxidation of xylo-oligosaccharides with degrees of polymerization greater than six. Whereas fusion to CtCBM22A did not alter the thermostability of GOOX-VN or reduce substrate inhibition, CtCBM22A_GOOX-VN could be immobilized to insoluble oat spelt xylan while retaining wild-type activity. QCM-D analysis showed that the fused enzyme remained bound during oxidation. These features could be harnessed to generate hemicellulose-based biosensors that detect and quantify the presence of different oligosaccharides. 相似文献
993.
994.
Molecular and Cellular Biochemistry - BMP10 plays an essential role in regulating cardiac growth, chamber maturation, and maintaining normal expressions of several key cardiogenic factors; however,... 相似文献
995.
996.
Tran Van Chien Tran Van Loc Nguyen The Anh Tran Van Sung Tran Thi Phuong Thao 《化学与生物多样性》2023,20(8):e202300420
A series of 3,19-isopropylidene-/or arylidene-andrographolide analogs were synthesized and their structures were confirmed by NMR spectroscopic methodology. Twenty-five analogs were evaluated for their in vitro cytotoxic activity against HT-29, HepG2 and LNCaP cancer cell lines based on the sulforhodamine B (SRB) assay. Analog 2 f exhibited the most potent cytotoxic activity, with IC50 values of 11.14 and 9.25 μM on HepG2 and LNCaP cancer cell lines, respectively. Esterification of hydroxy functional group at position C-14 in andrographolide analogs, 2 a and 2 b , showed somewhat higher cytotoxicity than the precursor. In addition, andrographolide analogs ( 2 a – 2 d , 2 f , 3 a , 4 a and 4 h ) were evaluated for the NO inhibitory activity in the LPS stimulated RAW264.7 macrophages. The most active analog 2 a significantly reduced nitric oxide (NO) production from LPS stimulated RAW264.7 cells, with IC50 values of 0.34±0.02 μM providing encouraging results for anti-inflammatory compound development. 相似文献
997.
Le Thi Thuy Le Huyen Tram Dinh Thi Phuong Anh Nguyen Thi Thuy My Nguyen Van Thong Nguyen Tuan Anh Dao Huy Toan Tran Thu Ha Bui Van Thanh Nguyen Thi Ngoc Mai Nguyen Ngoc Linh Duc-Dat Le Tran Thu Huong Nguyen Van Bach 《化学与生物多样性》2023,20(9):e202300904
A chemical investigation of K. heteroclite led to isolation of two new dibenzocyclooctadienes ( 1 and 2 ) together with 14 known compounds ( 3 – 16 ) by using multiple chromatographic techniques. New compounds ( 1 and 2 ) were obtained and identified by spectroscopic methods (HR-ESI-MS, 1D and 2D NMR, and ECD) as well as by comparison of their experimental data with those reported in the literatures. All the isolates were evaluated for their ability to modulate TNF-α production in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Among them, compound 5 displayed the most inhibition against tumor necrosis factor (TNF)-α production with IC50 value of 6.16±0.14 μM. Whereas, compounds ( 1 , 3 , and 6 ) showed the significant inhibition (IC50 values ranging from 9.41 to 14.54 μM), and compounds ( 2 , 4 , 9 , 10 , 13 , 15 , and 16 ) exhibited moderate inhibition (IC50 values ranging from 19.27 to 40.64 μM) toward TNF-α production, respectively. 相似文献
998.
Cyclodextrins and their derivatives have shown successful applications in extracting active compounds from medicinal plants. However, the use of β-cyclodextrin derivatives for extracting apigenin and luteolin from Chrysanthemum indicum L. remains unexplored. Additionally, the application of nature-inspired optimization algorithms in optimizing extraction conditions has been limited. Therefore, this study was performed with the aims of optimizing the extraction of apigenin and luteolin from C. indicum with the assistance of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) using response surface methodology combined with various optimization algorithms, including desirability function approach, genetic algorithm, particle swarm optimization, and firefly algorithm. The results showed that the optimal conditions obtained by the four algorithms were consistent, with an extraction time of 60 min, HP-β-CD concentration of 30 mg/mL, and a solvent-to-solid ratio of 24 mg/mL. At these conditions, the apigenin and luteolin contents were 1.362±0.008 and 8.724±0.117 mg/g, respectively. The results also showed that HP-β-CD-assisted extraction exhibited significantly higher apigenin and luteolin contents compared to conventional solvent. Comparable results were also yielded from the antioxidant assay. Our study suggested that the nature-inspired optimization algorithms might be potential options in enhancing the effectiveness of the traditional response surface methodology for the optimization of extraction of natural products. 相似文献
999.
Ali Andalibi Anh Diep Diana Quon Thuluvancheri Mohandas Benjamin A. Taylor Aldons J. Lusis 《Mammalian genome》1993,4(4):211-219
The prenyltransferases are a class of enzymes involved in the synthesis of sterol and nonsterol isoprene compounds. We report here the chromosomal mapping of nine loci in the mouse that hybridize to the cDNA for the enzyme farnesyl pyrophosphate synthetase (FPS), a prenyltransferase that catalyzes the synthesis of an intermediate common to both the sterol and nonsterol branches of the isoprene biosynthetic pathway. Mapping was performed with genomic DNA from a mouse-hamster somatic cell hybrid panel, and by linkage analysis with recombinant inbred strains and the progeny of an interspecific backcross. The mapped loci have been designated farnesyl pyrophosphate synthetase-like-1 (Fpsl-1) on mouse Chromosome (Chr) 3; Fpsl-2 on Chr 4; Fpsl-3, Fpsl-4, and Fpsl-5, dispersed on Chr 10; Fpsl-6 on Chr 12; Fpsl-7 on Chr 13; Fpsl-8 on Chr 17; and Fpsl-9 on Chr X. It is presently unclear which of these loci encode active prenyltransferases and which may correspond to pseudogenes. The strongly hybridizing loci provide convenient genetic markers for seven mouse chromosomes. 相似文献
1000.
George E. Taffet Thuy Thu Pham Diane L. M. Bick Mark L. Entman Henry J. Pownall Roger J. Bick 《The Journal of membrane biology》1993,131(1):35-42
Summary Small amounts of dietary n-3 fatty acids can have dramatic physiological effects, including the reduction of plasma triglycerides and an elevation of cellular eicosapentanoic (EPA) and docosahexanoic acids (DHA) at the expense of arachidonic acid (AA). We investigated the effects of alterations in the fatty acid compositions of cardiac sarcoplasmic reticulum (CSR) produced by dietary manipulation on the calcium pump protein that is required for energy dependent calcium transport. CSR was isolated from rats fed menhaden oil, which is rich in n-3 fatty acids, and from control animals that were given corn oil. Relative to control membranes, those isolated from rats fed menhaden oil, had a lower content of saturated phospholipids, an increased DHA/AA ratio, and an increased ratio of n-3 to n-6 fatty acids. These changes were associated with a 30% decrease in oxalate-facilitated, ATP-dependent calcium uptake and concomitant decreased Ca-ATPase activity in the membranes from the animals fed menhaden oil. In contrast, there was no alteration in active pump sites as measured by phosphoenzyme formation. Thus, the CSR Ca-ATPase function can be altered by dietary interventions that change the composition, and possibly structure, of the phospholipid membranes thereby affecting enzyme turnover. 相似文献