全文获取类型
收费全文 | 1254篇 |
免费 | 99篇 |
专业分类
1353篇 |
出版年
2023年 | 7篇 |
2022年 | 28篇 |
2021年 | 37篇 |
2020年 | 34篇 |
2019年 | 22篇 |
2018年 | 41篇 |
2017年 | 35篇 |
2016年 | 62篇 |
2015年 | 70篇 |
2014年 | 95篇 |
2013年 | 95篇 |
2012年 | 120篇 |
2011年 | 104篇 |
2010年 | 71篇 |
2009年 | 56篇 |
2008年 | 85篇 |
2007年 | 80篇 |
2006年 | 61篇 |
2005年 | 53篇 |
2004年 | 40篇 |
2003年 | 43篇 |
2002年 | 35篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1981年 | 4篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1972年 | 1篇 |
1957年 | 1篇 |
1956年 | 2篇 |
1954年 | 2篇 |
排序方式: 共有1353条查询结果,搜索用时 15 毫秒
101.
Identification and subcellular localization of paracellin-1 (claudin-16) in human salivary glands 总被引:2,自引:2,他引:0
Salivary calcium plays an important role in the pathogenesis of dental caries and the bio-mineralization of dental enamel and exposed dentin. The cellular and molecular basis of calcium secretion by the human salivary glands is, however, poorly understood. Recently a transcellular transport of calcium by the acinus cells has been proposed. In this paper we looked for evidence for paracellular calcium transport by investigating the presence and cellular localization of paracellin-1 (claudin-16) that has been implied in paracellular magnesium and calcium transport in the kidney. At the mRNA level, using RT-PCR with primers of appropriate sequence, paracellin-1 mRNA could be found in human Glandula parotis, Glandula submandibularis, Glandula labialis and Glandula sublingualis samples. In addition, a splice variant was detected in three out of 15 glands consisting of exons one and five of the paracellin gene. In immunohistochemical studies paracellin-1 colocalised in the salivary excretory ducts with the tight junction proteins ZO-1 and occludin suggesting a potential role in paracellular calcium and magnesium transport. In the acini no such colocalisation was observed; paracellin was instead detected at the basal poles of the cells, between cells of the same acinus as well as between cells of neighboring acini. At this location paracellin-1 might act as selectivity filter for the paracellular movement of ions and water during stimulated secretion. Thus, both in the ducts and in the acini a paracellular transport of calcium appears possible. Whether it occurs at all and the extent to which it contributes to the overall salivary calcium secretion remains, however, to be determined. 相似文献
102.
End-stacking of copper cationic porphyrins on parallel-stranded guanine quadruplexes 总被引:1,自引:0,他引:1
Sarah E. Evans Miguel A. Mendez Kevin B. Turner Loryn R. Keating Ryan T. Grimes Sarah Melchoir Veronika A. Szalai 《Journal of biological inorganic chemistry》2007,12(8):1235-1249
Nucleic acids that contain multiple sequential guanines assemble into guanine quadruplexes (G-quadruplexes). Drugs that induce or stabilize G-quadruplexes are of interest because of their potential use as therapeutics. Previously, we reported on the interaction of the Cu(2+) derivative of 5,10,15,20-tetrakis(1-methyl-4-pyridyl)-21H,23H-porphine (CuTMpyP4), with the parallel-stranded G-quadruplexes formed by d(T(4)G( n )T(4)) (n = 4 or 8) (Keating and Szalai in Biochemistry 43:15891-15900, 2004). Here we present further characterization of this system using a series of guanine-rich oligonucleotides: d(T(4)G( n )T(4)) (n = 5-10). Absorption titrations of CuTMpyP4 with all d(T(4)G( n )G(4)) quadruplexes produce approximately the same bathochromicity (8.3 +/- 2 nm) and hypochromicity (46.2-48.6%) of the porphyrin Soret band. Induced emission spectra of CuTMpyP4 with d(T(4)G( n )T(4))(4) quadruplexes indicate that the porphyrin is protected from solvent. Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry revealed a maximum porphyrin to quadruplex stoichiometry of 2:1 for the shortest (n = 4) and longest (n = 10) quadruplexes. Electron paramagnetic resonance spectroscopy shows that bound CuTMpyP4 occupies magnetically noninteracting sites on the quadruplexes. Consistent with our previous model for d(T(4)G(4)T(4)), we propose that two CuTMpyP4 molecules are externally stacked at each end of the run of guanines in all d(T(4)G( n )T(4)) (n = 4-10) quadruplexes. 相似文献
103.
Vezenkov Lyubomir T. Danalev Dancho L. Iwanov Iwan Lozanov Valentin Atanasov Atanas Todorova Rumyana Vassilev Nikolay Karadjova Veronika 《Amino acids》2022,54(6):897-910
Amino Acids - The Alzheimer’s disease leads to neurodegenerative processes and affecting negatively million people worldwide. The treatment of the disease is still difficult and incomplete in... 相似文献
104.
Steffen Heelemann Veronika Bäuerlein Cornelia B. Krug Karen J. Esler Peter Poschlod Christoph Reisch 《African Journal of Ecology》2015,53(4):447-453
We tested the effects of life‐history traits on genetic variation and conducted a comparative analysis of two plant species with differing life‐history traits co‐occurring in the highly endangered renosterveld of South Africa. We selected eighteen renosterveld remnants with varying degrees of size and isolation where populations of the herbaceous, annual and insect‐pollinated Hemimeris racemosa and the shrubby perennial and both wind‐ and insect‐pollinated Eriocephalus africanus occurred. We postulated a lower genetic variation within populations and increased genetic variation between populations in the annual than in the perennial species. Genetic variation was lower within populations of H. racemosa than within E. africanus, as is typical for annual compared to perennial species. Variation within populations was, however, not correlated with fragment size or distance in either of the two species and genetic variation between populations of the two species was comparable (ΦST = 0.10, 0.09). 相似文献
105.
106.
107.
108.
Jarrod A Chapman Martin Mascher Ayd?n Bulu? Kerrie Barry Evangelos Georganas Adam Session Veronika Strnadova Jerry Jenkins Sunish Sehgal Leonid Oliker Jeremy Schmutz Katherine A Yelick Uwe Scholz Robbie Waugh Jesse A Poland Gary J Muehlbauer Nils Stein Daniel S Rokhsar 《Genome biology》2015,16(1)
Polyploid species have long been thought to be recalcitrant to whole-genome assembly. By combining high-throughput sequencing, recent developments in parallel computing, and genetic mapping, we derive, de novo, a sequence assembly representing 9.1 Gbp of the highly repetitive 16 Gbp genome of hexaploid wheat, Triticum aestivum, and assign 7.1 Gb of this assembly to chromosomal locations. The genome representation and accuracy of our assembly is comparable or even exceeds that of a chromosome-by-chromosome shotgun assembly. Our assembly and mapping strategy uses only short read sequencing technology and is applicable to any species where it is possible to construct a mapping population.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0582-8) contains supplementary material, which is available to authorized users. 相似文献109.
Korabecny J Musilek K Zemek F Horova A Holas O Nepovimova E Opletalova V Hroudova J Fisar Z Jung YS Kuca K 《Bioorganic & medicinal chemistry letters》2011,21(21):6563-6566
Cholinesterase inhibitors are, so far, the only successful strategy for the symptomatic treatment of Alzheimer's disease. Tacrine (THA) is a potent acetylcholinesterase inhibitor that was used in the treatment of Alzheimer's disease for a long time. However, the clinical use of THA was hampered by its low therapeutic index, short half-life and liver toxicity. 7-Methoxytacrine (7-MEOTA) is equally pharmacological active compound with lower toxicity compared to THA. In this Letter, the synthesis, biological activity and molecular modelling of elimination by-product isolated during synthesis of 7-MEOTA based bis-alkylene linked compound is described. 相似文献
110.
Chase GP Rameix-Welti MA Zvirbliene A Zvirblis G Götz V Wolff T Naffakh N Schwemmle M 《PLoS pathogens》2011,7(9):e1002187
In contrast to most RNA viruses, influenza viruses replicate their genome in the nucleus of infected cells. As a result, newly-synthesized vRNA genomes, in the form of viral ribonucleoprotein complexes (vRNPs), must be exported to the cytoplasm for productive infection. To characterize the composition of vRNP export complexes and their interplay with the nucleus of infected cells, we affinity-purified tagged vRNPs from biochemically fractionated infected nuclei. After treatment of infected cells with leptomycin B, a potent inhibitor of Crm1-mediated export, we isolated vRNP export complexes which, unexpectedly, were tethered to the host-cell chromatin with very high affinity. At late time points of infection, the cellular export receptor Crm1 also accumulated at the same regions of the chromatin as vRNPs, which led to a decrease in the export of other nuclear Crm1 substrates from the nucleus. Interestingly, chromatin targeting of vRNP export complexes brought them into association with Rcc1, the Ran guanine exchange factor responsible for generating RanGTP and driving Crm1-dependent nuclear export. Thus, influenza viruses gain preferential access to newly-generated host cell export machinery by targeting vRNP export complexes at the sites of Ran regeneration. 相似文献