全文获取类型
收费全文 | 771篇 |
免费 | 52篇 |
国内免费 | 2篇 |
专业分类
825篇 |
出版年
2022年 | 8篇 |
2021年 | 9篇 |
2020年 | 4篇 |
2019年 | 6篇 |
2018年 | 12篇 |
2017年 | 5篇 |
2016年 | 11篇 |
2015年 | 18篇 |
2014年 | 27篇 |
2013年 | 31篇 |
2012年 | 40篇 |
2011年 | 42篇 |
2010年 | 33篇 |
2009年 | 26篇 |
2008年 | 60篇 |
2007年 | 40篇 |
2006年 | 44篇 |
2005年 | 43篇 |
2004年 | 36篇 |
2003年 | 48篇 |
2002年 | 55篇 |
2001年 | 12篇 |
2000年 | 6篇 |
1999年 | 12篇 |
1998年 | 16篇 |
1997年 | 11篇 |
1996年 | 8篇 |
1995年 | 12篇 |
1994年 | 6篇 |
1993年 | 11篇 |
1992年 | 12篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 10篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 6篇 |
1985年 | 4篇 |
1984年 | 11篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 9篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1974年 | 6篇 |
1973年 | 8篇 |
1971年 | 6篇 |
排序方式: 共有825条查询结果,搜索用时 15 毫秒
71.
Oszvald M Kang TJ Tomoskozi S Tamas C Tamas L Kim TG Yang MS 《Molecular biotechnology》2007,35(3):215-223
Epitopes often require co-delivery with adjuvant and targeting proteins to enable recognition by the immune system, and this approach may also increase the efficacy of the antigen. In this study, we assess and describe the ability of transgenic rice plants to express a fusion protein consisting of the B-subunit of the Escherichia coli heat-labile enterotoxin (LTB) and a synthetic core-neutralizing epitope (COE) of porcine epidemic diarrhea virus (PEDV), inducing an enteric disease that is seen most predominantly in piglets. Both components of the fusion proteins were detected with Western blot analysis. The fusion protein was determined to assemble into pentamers, as was evidenced by its ability to bind to GM1 gangliosides, and evidenced an average level of expression in a transgenic rice endosperm. This indicates that the expression system of the plant is capable of generating a sizable amount of antigen, possibly allowing for the successful development of an edible vaccine. 相似文献
72.
73.
74.
Gaware R Khunt R Czollner L Stanetty C Da Cunha T Kratschmar DV Odermatt A Kosma P Jordis U Classen-Houben D 《Bioorganic & medicinal chemistry》2011,19(6):1866-1880
Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and type 2. Whereas inhibition of 11β-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11β-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11β-HSD2. The most potent and selective compound is active against human 11β-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11β-HSD1. Starting from the lead compounds glycyrrhetinic acid and the hydroxamic acid derivatives, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11β-HSD1 and 11β-HSD2 in cell lysates. Here we describe novel 29-urea- and 29-hydroxamic acid derivatives of glycyrrhetinic acid as well as derivatives with the Beckman rearrangement of the 3-oxime to a seven-membered ring, and the rearrangement of the C-ring from 11-keto-12-ene to 12-keto-9(11)-ene. The combination of modifications on different positions led to compounds comprising further improved selective inhibition of 11β-HSD2 in the lower nanomolar range with up to 3600-fold selectivity. 相似文献
75.
Gyenis L Duncan JS Turowec JP Bretner M Litchfield DW 《Journal of proteome research》2011,10(11):4887-4901
Protein kinases have emerged as attractive targets for treatment of several diseases prompting large-scale phosphoproteomics studies to elucidate their cellular actions and the design of novel inhibitory compounds. Current limitations include extensive reliance on consensus predictions to derive kinase-substrate relationships from phosphoproteomics data and incomplete experimental validation of inhibitors. To overcome these limitations in the case of protein kinase CK2, we employed functional proteomics and chemical genetics to enable identification of physiological CK2 substrates and validation of CK2 inhibitors including TBB and derivatives. By 2D electrophoresis and mass spectrometry, we identified the translational elongation factor EEF1D as a protein exhibiting CK2 inhibitor-dependent decreases in phosphorylation in (32)P-labeled HeLa cells. Direct phosphorylation of EEF1D by CK2 was shown by performing CK2 assays with EEF1D -FLAG from HeLa cells. Dramatic increases in EEF1D phosphorylation following λ-phosphatase treatment and phospho- EEF1D antibody recognizing EEF1D pS162 indicated phosphorylation at the CK2 site in cells. Furthermore, phosphorylation of EEF1D in the presence of TBB or TBBz is restored using CK2 inhibitor-resistant mutants. Collectively, our results demonstrate that EEF1D is a bona fide physiological CK2 substrate for CK2 phosphorylation. Furthermore, this validation strategy could be adaptable to other protein kinases and readily combined with other phosphoproteomic methods. 相似文献
76.
Szabo A Balog M Mark L Montsko G Turi Z Gallyas F Sumegi B Kalai T Hideg K Kovacs K 《Mitochondrion》2011,11(3):476-487
In this paper, we present evidence, for the first time, that increasing the lipophilicity of mitochondria targeting SOD mimetics reverses their cytoprotective properties, destabilizing the mitochondrial membrane system and promoting cell death. A new mitochondria-directed apolar SOD mimetic, HO-3814, was found to provoke mitochondrial swelling and loss of mitochondrial membrane potential, and these effects were not inhibited by cyclosporine A. HO-3814-induced cell death was predominantly necrotic, caspase-independent, and not affected by mitochondrial permeability transition inhibitors or cyclophilin D-suppression, inhibitors of mitogen-activated protein kinases or Akt, or various antioxidants. In contrast, Bcl-2 overexpression diminished the effects of HO-3814. 相似文献
77.
78.
Copeland A O'Connor K Lucas S Lapidus A Berry KW Detter JC Del Rio TG Hammon N Dalin E Tice H Pitluck S Bruce D Goodwin L Han C Tapia R Saunders E Schmutz J Brettin T Larimer F Land M Hauser L Vargas C Nieto JJ Kyrpides NC Ivanova N Göker M Klenk HP Csonka LN Woyke T 《Standards in genomic sciences》2011,5(3):379-388
Chromohalobacter salexigens is one of nine currently known species of the genus Chromohalobacter in the family Halomonadaceae. It is the most halotolerant of the so-called 'moderately halophilic bacteria' currently known and, due to its strong euryhaline phenotype, it is an established model organism for prokaryotic osmoadaptation. C. salexigens strain 1H11(T) and Halomonas elongata are the first and the second members of the family Halomonadaceae with a completely sequenced genome. The 3,696,649 bp long chromosome with a total of 3,319 protein-coding and 93 RNA genes was sequenced as part of the DOE Joint Genome Institute Program DOEM 2004. 相似文献
79.
A variant of KCC2 from patients with febrile seizures impairs neuronal Cl− extrusion and dendritic spine formation 下载免费PDF全文
Martin Puskarjov Patricia Seja Sarah E Heron Tristiana C Williams Faraz Ahmad Xenia Iona Karen L Oliver Bronwyn E Grinton Laszlo Vutskits Ingrid E Scheffer Steven Petrou Peter Blaesse Leanne M Dibbens Samuel F Berkovic Kai Kaila 《EMBO reports》2014,15(6):723-729
Genetic variation in SLC12A5 which encodes KCC2, the neuron-specific cation-chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co-segregating variant (KCC2-R952H) in an Australian family with febrile seizures. We show that KCC2-R952H reduces neuronal Cl− extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2-R952H which likely contributes to the functional deficits. Our data suggest that KCC2-R952H is a bona fide susceptibility variant for febrile seizures. 相似文献
80.
Judit Kapocsi George T. Somogyi Nandor Ludvig Peter Serfozo Laszlo G. Harsing Jr. Russell J. Woods E. Sylvester Vizi 《Neurochemical research》1987,12(2):141-147
Neurochemical and pharmacological evidence has been obtained that noradrenergic varicosities (in mouse and rat vas deferens) and cholinergic varicosities (in the Auerbach's plexus) contain heterogenous alpha2-adrenoceptors through which the release of [3H]noradrenaline and [3H]acetylcholine can be modulated. The quantitative data also support the hypothesis that different noradrenaline and xylazine sensitive alpha2-adrenoceptors are present prejunctionally in the vas deferens and Auerbach's plexus preparations. Prazosin, although it has a presynaptic inhibitory effect on alpha2-adrenoceptors of noradrenergic axon terminals, has no effect on cholinergic axon terminals. These data suggest that there are two different types of alpha2-adrenoceptors at the presynaptic axon terminals.Special Issue Dedicated to Dr. Abel Lajtha 相似文献