全文获取类型
收费全文 | 2040篇 |
免费 | 200篇 |
出版年
2024年 | 2篇 |
2023年 | 9篇 |
2022年 | 20篇 |
2021年 | 58篇 |
2020年 | 39篇 |
2019年 | 34篇 |
2018年 | 40篇 |
2017年 | 32篇 |
2016年 | 69篇 |
2015年 | 109篇 |
2014年 | 108篇 |
2013年 | 150篇 |
2012年 | 193篇 |
2011年 | 176篇 |
2010年 | 111篇 |
2009年 | 98篇 |
2008年 | 144篇 |
2007年 | 141篇 |
2006年 | 134篇 |
2005年 | 126篇 |
2004年 | 105篇 |
2003年 | 99篇 |
2002年 | 77篇 |
2001年 | 14篇 |
2000年 | 14篇 |
1999年 | 16篇 |
1998年 | 19篇 |
1997年 | 8篇 |
1996年 | 9篇 |
1995年 | 7篇 |
1994年 | 11篇 |
1993年 | 9篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有2240条查询结果,搜索用时 203 毫秒
71.
72.
73.
Ronja Breitkopf Ronny Uhlig Tina Drenckhan Ralf-Jörg Fischer 《Extremophiles : life under extreme conditions》2016,20(5):653-661
Moorella thermoacetica is one of the model acetogenic bacteria for the resolution of the Wood–Ljungdahl (acetyl-CoA) pathway in which CO2 is autotrophically assimilated yielding acetyl-CoA as central intermediate. Its further conversion into acetate relies on subsequent phosphotransacetylase (PTA) and acetate kinase reactions. However, the genome of M. thermoacetica contains no pta homologous gene. It has been speculated that the moth_0864 and moth_1181 gene products sharing similarities with an evolutionarily distinct phosphotransacylase involved in 1,2-propanediol utilization (PDUL) of Salmonella enterica act as PTAs in M. thermoacetica. Here, we demonstrate specific PTA activities with acetyl-CoA as substrate of 9.05 and 2.03 U/mg for the recombinant enzymes PDUL1 (Moth_1181) and PDUL2 (Moth_0864), respectively. Both showed maximal activity at 65 °C and pH 7.6. Native proteins (90 kDa) are homotetramers composed of four subunits with apparent molecular masses of about 23 kDa. Thus, one or both PDULs of M. thermoacetica might act as PTAs in vivo catalyzing the penultimate step of the Wood–Ljungdahl pathway toward the formation of acetate. In silico analysis underlined that up to now beside of M. thermoacetica, only Sporomusa ovata contains only PDUL like classIII-PTAs but no other phosphotransacetylases or phosphotransbutyrylases (PTBs). 相似文献
74.
Fatemeh Norozi Javad Mohammadi-asl Tina Vosoughi Mohammad Ali Jalali Far Amal Saki Malehi Najmaldin Saki 《生物学前沿》2016,11(5):404-411
Objectives
Targeted therapy of Philadelphia-positive ALL and CML patients using imatinib (IM) has caused significant changes in treatment course and has increased the survival of patients. A small group of patients show resistance to IM. Acquired mutations in tyrosine kinase domain of BCR-ABL protein are a mechanism for development of resistance. T315I is one of the most common acquired mutations in this domain, which occurs in ATP binding site and inhibits the formation of hydrogen bond with IM. The aim of this study was to evaluate the prevalence of this mutation in BCR/ABL-positive CML and ALL patients.Methods
To conduct this study, 60 BCR-ABL-positive patients (including 50 CML and 10 ALL patients) who were subject to treatment with IM were selected. After taking the samples, presence of T315I mutation was assessed using ARMS-PCR on cDNA and its polymorphism was evaluated by sequencing.Results
The results showed that among 60 patients, only three patients had T315I mutation, which was detected using ARMS technique. The three patients bearing mutation were afflicted with CML and no significant association was found between blood parameters with duration of treatment in presence of mutation.Conclusions
The mutation was found in three CML patients, which indicated lower likelihood and diagnostic value of this mutation in ALL patients. Given the negative direct sequencing results in T315I patients, it can be concluded that ARMS-PCR is a more sensitive technique when the number of cancer cells is low in patients during treatment.75.
Christopher B. Cooper Edward J. Beard lvaro Vzquez‐Mayagoitia Liliana Stan Gavin B. G. Stenning Daniel W. Nye Julian A. Vigil Tina Tomar Jingwen Jia Govardhana B. Bodedla Song Chen Lucía Gallego Santiago Franco Antonio Carella K. R. Justin Thomas Song Xue Xunjin Zhu Jacqueline M. Cole 《Liver Transplantation》2019,9(5)
Data‐driven materials discovery has become increasingly important in identifying materials that exhibit specific, desirable properties from a vast chemical search space. Synergic prediction and experimental validation are needed to accelerate scientific advances related to critical societal applications. A design‐to‐device study that uses high‐throughput screens with algorithmic encodings of structure–property relationships is reported to identify new materials with panchromatic optical absorption, whose photovoltaic device applications are then experimentally verified. The data‐mining methods source 9431 dye candidates, which are auto‐generated from the literature using a custom text‐mining tool. These candidates are sifted via a data‐mining workflow that is tailored to identify optimal combinations of organic dyes that have complementary optical absorption properties such that they can harvest all available sunlight when acting as co‐sensitizers for dye‐sensitized solar cells (DSSCs). Six promising dye combinations are shortlisted for device testing, whereupon one dye combination yields co‐sensitized DSSCs with power conversion efficiencies comparable to those of the high‐performance, organometallic dye, N719. These results demonstrate how data‐driven molecular engineering can accelerate materials discovery for panchromatic photovoltaic or other applications. 相似文献
76.
Christopher B. Cooper Edward J. Beard lvaro Vzquez‐Mayagoitia Liliana Stan Gavin B. G. Stenning Daniel W. Nye Julian A. Vigil Tina Tomar Jingwen Jia Govardhana B. Bodedla Song Chen Lucía Gallego Santiago Franco Antonio Carella K. R. Justin Thomas Song Xue Xunjin Zhu Jacqueline M. Cole 《Liver Transplantation》2019,9(5)
77.
78.
79.
Wenz T Covian R Hellwig P Macmillan F Meunier B Trumpower BL Hunte C 《The Journal of biological chemistry》2007,282(6):3977-3988
The cytochrome bc1 complex is a dimeric enzyme of the inner mitochondrial membrane that links electron transfer from ubiquinol to cytochrome c by a protonmotive Q cycle mechanism in which ubiquinol is oxidized at one center in the enzyme, referred to as center P, and ubiquinone is rereduced at a second center, referred to as center N. To better understand the mechanism of ubiquinol oxidation, we have examined catalytic activities and pre-steady-state reduction kinetics of yeast cytochrome bc1 complexes with mutations in cytochrome b that we expected would affect oxidation of ubiquinol. We mutated two residues thought to be involved in proton conduction linked to ubiquinol oxidation, Tyr132 and Glu272, and two residues proposed to be involved in docking ubiquinol into the center P pocket, Phe129 and Tyr279. Substitution of Phe129 by lysine or arginine yielded a respiration-deficient phenotype and lipid-dependent catalytic activity. Increased bypass reactions were detectable for both variants, with F129K showing the more severe effects. Substitution with lysine leads to a disturbed coordination of a b heme as deduced from changes in the midpoint potential and the EPR signature. Removal of the aromatic side chain in position Tyr279 lowers the catalytic activity accompanied by a low level of bypass reactions. Pre-steady-state kinetics of the enzymes modified at Glu272 and Tyr132 confirmed the importance of their functional groups for electron transfer. Altered center N kinetics and activation of ubiquinol oxidation by binding of cytochrome c in the Y132F and E272D enzymes indicate long range effects of these mutations. 相似文献
80.
Intranuclear inclusion bodies (IBs) are the histopathologic markers of multiple protein folding diseases. IB formation has been extensively studied using fluorescent fusion products of pathogenic polyglutamine (polyQ) expressing proteins. These studies have been informative in determining the cellular targets of expanded polyQ protein as well as the methods by which cells rid themselves of IBs. The experimental thrust has been to intervene in the process of polyQ aggregation in an attempt to alleviate cytotoxicity. However new data argues against the notion that polyQ aggregation and cytotoxicity are inextricably linked processes. We reasoned that changing the protein context of a disease causing polyQ protein could accelerate its precipitation as an IB, potentially reducing its cytotoxicity. Our experimental strategy simply exploited the fact that conjoined proteins influence each others folding and aggregation properties. We fused a full-length pathogenic ataxin-1 construct to fluorescent tags (GFP and DsRed1-E5) that exist at different oligomeric states. The spectral properties of the DsRed1-E5-ataxin-1 transfectants had the additional advantage of allowing us to correlate fluorochrome maturation with cytotoxicity. Each fusion protein expressed a distinct cytotoxicity and IB morphology. Flow cytometric analyses of transfectants expressing the greatest fluorescent signals revealed that the DsRed1-E5-ataxin-1 fusion was more toxic than GFP fused ataxin-1 (31.8+/-4.5% cell death versus 12.85+/-3%), although co-transfection with the GFP fusion inhibited maturation of the DsRed1-E5 fluorochrome and diminished the toxicity of the DsRed1-E5-ataxin-1 fusion. These data show that polyQ driven aggregation can be influenced by fusion partners to generate species with different toxic properties and provide new opportunities to study IB aggregation, maturation and lethality. 相似文献