全文获取类型
收费全文 | 421篇 |
免费 | 35篇 |
出版年
2023年 | 4篇 |
2022年 | 1篇 |
2021年 | 19篇 |
2020年 | 6篇 |
2019年 | 12篇 |
2018年 | 19篇 |
2017年 | 7篇 |
2016年 | 19篇 |
2015年 | 15篇 |
2014年 | 23篇 |
2013年 | 31篇 |
2012年 | 38篇 |
2011年 | 39篇 |
2010年 | 20篇 |
2009年 | 20篇 |
2008年 | 34篇 |
2007年 | 16篇 |
2006年 | 15篇 |
2005年 | 31篇 |
2004年 | 16篇 |
2003年 | 17篇 |
2002年 | 16篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有456条查询结果,搜索用时 421 毫秒
61.
62.
63.
Supriya Chakraborty Swatilekha Ghosh Bhaswati Banerjee Abhishek Santra Jyotsna Bhat Arghya Adhikary Subhrangsu Chatterjee Anup K. Misra Parimal C. Sen 《Apoptosis : an international journal on programmed cell death》2016,21(10):1106-1124
The efficacy of cancer chemotherapeutics is limited by side effects resulting from narrow therapeutic windows between the anticancer activity of a drug and its cytotoxicity. Thus identification of small molecules that can selectively target cancer cells has gained major interest. Cancer cells under stress utilize the Unfolded protein response (UPR) as an effective cell adaptation mechanism. The purpose of the UPR is to balance the ER folding environment and calcium homeostasis under stress. If ER stress is prolonged, tumor cells undergo apoptosis. In the present study we demonstrated an 3,3′-(Arylmethylene)-bis-1H-indole (AMBI) derivative 3,3′-[(4-Methoxyphenyl) methylene]-bis-(5-bromo-1H-indole), named as Mephebrindole (MPB) as an effective anti-cancer agent in breast cancer cells. MPB disrupted calcium homeostasis in MCF7 cells which triggered ER stress development. Detailed evaluations revealed that mephebrindole by activating p38MAPK also regulated GRP78 and eIF2α/ATF4 downstream to promote apoptosis. Studies extended to in vivo allograft mice models revalidated its anti-carcinogenic property thus highlighting the role of MPB as an improved chemotherapeutic option. 相似文献
64.
The high level expression and purification of rat monoamine oxidase B (rMAOB) in the methylotrophic yeast Pichia pastoris is reported. Nearly 100 mg of purified rMAOB is obtained from 130 g (wet weight) of cells (0.5 L of culture). The MALDI-TOF mass spectrum of the purified protein shows a single species with a molecular mass of 59.228 ± 0.064 kDa, which agrees with the calculated molecular weight of 59.172 kDa for the rMAOB protein sequence assuming one mole of covalent FAD per mole of the enzyme. Consistent with the MALDI-MS data, purified rMAOB shows a single band near 60 kDa in Coomassie-stained SDS–PAGE gel as well as on Western blot analyses performed using antisera raised against human MAOA and BSA-conjugated FAD. A partial amino acid sequence of the purified protein is confirmed to be that of the wild type rMAOB by in-gel trypsin digestion and MALDI-TOF-MS analyses of the liberated peptide fragments. Steady state kinetic data show that purified rMAOB exhibits a Km(amine) of 176 ± 15 μM and a kcat of 497 ± 83 min−1 for benzylamine oxidation, and a Km(O2) of 170 ± 10 μM. Kinetic parameters obtained for purified rMAOB are compared with those reported earlier for recombinant human liver MAOB expressed in P. pastoris. 相似文献
65.
66.
Ghosh S Tiwari P Pandey S Misra AK Chaturvedi V Gaikwad A Bhatnagar S Sinha S 《Bioorganic & medicinal chemistry letters》2008,18(14):4002-4005
A series of glycosyl thioacetamide and glycosyl sulfonyl acetamide derivatives have been prepared following a convenient reaction protocol and evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv. Amongst 32 compounds evaluated 3 compounds were effective in inhibiting mycobacterial growth at MIC of 6.25 μg/mL, 6 compounds at MIC of 3.125 μg/mL and 1 compound at MIC of 1.56 μg/mL. All active compounds were found nontoxic in Vero cell lines and mice bone marrow macrophages. 相似文献
67.
Samir Ghosh Anup Kumar Misra Gitika Bhatia M.M. Khan A.K. Khanna 《Bioorganic & medicinal chemistry letters》2009,19(2):386-389
A series of N-per-O-acetyl-glucosyl arylthiosemicarbazide and thiosemicarbazone derivatives have been synthesized and evaluated for their in vivo anti-dyslipidemic and in vitro antioxidant activities. Among 16 compounds tested, 3 compounds showed potent anti-dyslipidemic activity and 6 compounds showed potent antioxidant and scavenger of oxygen free radicals activity. 相似文献
68.
Arkadeb Dutta Praveen Vats Vijay K. Singh Yogendra K. Sharma Som N. Singh Shashi B. Singh 《International journal of biometeorology》2009,53(5):397-407
Mitochondrial ß-oxidation of fatty acid provides a major source of energy in mammals. High altitude (HA), characterized by hypobaric hypoxia and low ambient temperatures, causes alteration in metabolic homeostasis. Several studies have depicted that hypoxic exposure in small mammals causes hypothermia due to hypometabolic state. Moreover, cold exposure along with hypoxia reduces hypoxia tolerance in animals. The present study investigated the rate of β-oxidation and key enzymes, carnitine palmitoyl transferase-I (CPT-I) and hydroxyacyl CoA dehydrogenase (HAD), in rats exposed to cold-hypobaric hypoxic environment. Male Sprague Dawley rats (190–220 g) were randomly divided into eight groups (n?=?6 rats in each group): 1 day hypoxia (H1); 7 days hypoxia (H7); 1 day cold (C1); 7 days cold (C7); 1 day cold-hypoxia (CH1); 7 days cold-hypoxia (CH7) exposed; and unexposed control for 1 and 7 days (UC1 and UC7). After exposure, animals were anaesthetized with ketamine (50 mg/kg body weight) and xylazine (10 mg/kg body weight) intraperitonialy and sacrificed. Mitochondrial CPT-I, HAD, 14C-palmitate oxidation in gastrocnemius muscle and liver, and plasma leptin were measured. Mitochondrial CPT-I was significantly reduced in muscle and liver in CH1 and CH7 as compared to respective controls. HAD activity was significantly reduced in H1 and CH7, and in H1, H7, CH1, and CH7 as compared to unexposed controls in muscle and liver, respectively. A concomitant decrease in 14C-palmitate oxidation was found. Significant reduction in plasma leptin in hypoxia and cold-hypoxia suggested hypometabolic state. It can be concluded that ß-oxidation of fatty acids is reduced in rats exposed to cold-hypoxic environment due to the persisting hypometabolic state in cold-hypoxia exposure. 相似文献
69.
Gareth A. Palidwor Sergey Shcherbinin Matthew R. Huska Tamas Rasko Ulrich Stelzl Anup Arumughan Raphaele Foulle Pablo Porras Luis Sanchez-Pulido Erich E. Wanker Miguel A. Andrade-Navarro 《PLoS computational biology》2009,5(3)
A growing number of solved protein structures display an elongated structural
domain, denoted here as alpha-rod, composed of stacked pairs of anti-parallel
alpha-helices. Alpha-rods are flexible and expose a large surface, which makes
them suitable for protein interaction. Although most likely originating by
tandem duplication of a two-helix unit, their detection using sequence
similarity between repeats is poor. Here, we show that alpha-rod repeats can be
detected using a neural network. The network detects more repeats than are
identified by domain databases using multiple profiles, with a low level of
false positives (<10%). We identify alpha-rod repeats in
approximately 0.4% of proteins in eukaryotic genomes. We then
investigate the results for all human proteins, identifying alpha-rod repeats
for the first time in six protein families, including proteins STAG1-3, SERAC1,
and PSMD1-2 & 5. We also characterize a short version of these repeats
in eight protein families of Archaeal, Bacterial, and Fungal species. Finally,
we demonstrate the utility of these predictions in directing experimental work
to demarcate three alpha-rods in huntingtin, a protein mutated in
Huntington''s disease. Using yeast two hybrid analysis and an
immunoprecipitation technique, we show that the huntingtin fragments containing
alpha-rods associate with each other. This is the first definition of domains in
huntingtin and the first validation of predicted interactions between fragments
of huntingtin, which sets up directions toward functional characterization of
this protein. An implementation of the repeat detection algorithm is available
as a Web server with a simple graphical output: http://www.ogic.ca/projects/ard. This can be further visualized
using BiasViz, a graphic tool for representation of multiple sequence
alignments. 相似文献
70.
Anup Parikh Eryong Huang Christopher Dinh Blaz Zupan Adam Kuspa Devika Subramanian Gad Shaulsky 《BMC bioinformatics》2010,11(1):163