全文获取类型
收费全文 | 1560篇 |
免费 | 107篇 |
出版年
2023年 | 5篇 |
2022年 | 12篇 |
2021年 | 43篇 |
2020年 | 24篇 |
2019年 | 22篇 |
2018年 | 32篇 |
2017年 | 35篇 |
2016年 | 59篇 |
2015年 | 79篇 |
2014年 | 91篇 |
2013年 | 121篇 |
2012年 | 145篇 |
2011年 | 133篇 |
2010年 | 84篇 |
2009年 | 71篇 |
2008年 | 95篇 |
2007年 | 79篇 |
2006年 | 102篇 |
2005年 | 71篇 |
2004年 | 90篇 |
2003年 | 74篇 |
2002年 | 59篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 13篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 8篇 |
1995年 | 14篇 |
1994年 | 7篇 |
1993年 | 9篇 |
1992年 | 8篇 |
1991年 | 6篇 |
1990年 | 7篇 |
1989年 | 3篇 |
1987年 | 4篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 5篇 |
1982年 | 1篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1961年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有1667条查询结果,搜索用时 850 毫秒
401.
Stefanie D. Krämer Dario Lombardi Adriana Primorac Anita V. Thomae Heidi Wunderli‐Allenspach 《化学与生物多样性》2009,6(11):1900-1916
Lipid‐bilayer permeation is determinant for the disposition of xenobiotics in the body. It controls the pharmacokinetic behavior of drugs and is, in many cases, a prerequisite for intracellular targeting. Permeation of in vivo barriers is in general predicted from lipophilicity and related parameters. This article goes beyond the empirical correlations, and elucidates the processes and their interplay determining bilayer permeation. A flip‐flop model for bilayer permeation, which considers the partitioning rate constants beside the translocation rate constants, is compared with the diffusion model based on Fick's first law. According to the flip‐flop model, the ratios of aqueous volumes to barrier area can determine whether partitioning or translocation is rate‐limiting. The flip‐flop model allows permeation of anions and cations, and expands our understanding of pH‐dependent permeation kinetics. Some experimental evidences for ion‐controlled permeation at pH 7 are also included in this work. 相似文献
402.
Elena Cassani Edoardo Bertolini Francesco Cerino Badone Michela Landoni Dario Gavina Alberto Sirizzotti Roberto Pilu 《Molecular breeding : new strategies in plant improvement》2009,24(4):375-385
The “green revolution” involving mainly wheat and rice was based on the use by breeders of semidominant mutations involved
in the signal transduction pathway of Gibberellin (GA). In particular, mutations in the Reduced height (Rht) gene of wheat have been used to reduce plant height and consequently to avoid storm damage and lodging. These genes have
been cloned and they encode for DELLA proteins which contain an N-terminal DELLA and a VHYNP domain essential for GA-dependent
degradation of these proteins. In maize several mutations have been isolated which affect gibberellin biosynthesis and perception
and in particular, mutations in Dwarf8 (D8) gene cause a severe dwarfing phenotype. D8 gene has been identified as an orthologue of Rht (Reduced height), Slr1(Slender rice 1) and Gibberellic Acid Insensitive (GAI) genes, this latter is a negative regulator of GA response in Arabidopsis. In this work, for the first time, we isolated and characterized a single amino acid insertion in the VHYNP domain of D8 maize gene causing the appearance of a dominant dwarf mutation. This spontaneous mutation, named D8-1023, showed a phenotype which is less severe in comparison with the other D8 mutants previously isolated which have modifications
in the DELLA domain. This mutant appears to be an useful tool either to study the mechanism of GA-modulated growth in plants
or to lower the height of maize tropical germplasm for breeding purposes. 相似文献
403.
Daviña JR Grabiele M Cerutti JC Hojsgaard DH Almada RD Insaurralde IS Honfi AI 《Genetics and molecular biology》2009,32(4):811-821
The center of diversity of Argentinean orchids is in the northeast region of the country. Chromosome numbers and karyotype features of 43 species belonging to 28 genera are presented here. Five chromosome records are the first ones at the genus level; these taxa are Aspidogyne kuckzinskii (2n = 42), Eurystyles actinosophila (2n = 56), Skeptrostachys paraguayensis (2n = 46), Stigmatosema polyaden (2n = 40) and Zygostates alleniana (2n = 54). In addition, a chromosome number is presented for the first time for 15 species: Corymborkis flava (2n = 56), Cyclopogon callophyllus (2n = 28), C. oliganthus (2n = 64), Cyrtopodium hatschbachii (2n = 46), C. palmifrons (2n = 46), Galeandra beyrichii (2n = 54), Habenaria bractescens (2n = 44), Oncidium edwallii (2n = 42), O. fimbriatum (2n = 56), O. pubes (2n = 84), O. riograndense (2n = 56), Pelexia ekmanii (2n = 46), P. lindmanii (2n = 46) and Warrea warreana (2n = 48). For Oncidium longicornu (2n = 42), O. divaricatum (2n = 56) and Sarcoglottis fasciculata (2n = 46+1B?, 46+3B?), a new cytotype was found. Chromosome data support phylogenetic relationships proposed by previous cytological, morphologic and molecular analyses, and in all the cases cover some gaps in the South American literature on orchid chromosomes. 相似文献
404.
Arhin F Bélanger O Ciblat S Dehbi M Delorme D Dietrich E Dixit D Lafontaine Y Lehoux D Liu J McKay GA Moeck G Reddy R Rose Y Srikumar R Tanaka KS Williams DM Gros P Pelletier J Parr TR Far AR 《Bioorganic & medicinal chemistry》2006,14(17):5812-5832
The RNA polymerase holoenzyme is a proven target for antibacterial agents. A high-throughput screening program based on this enzyme from Staphylococcus aureus had previously identified a 2-ureidothiophene-3-carboxylate as a low micromolar inhibitor. An investigation of the relationships between the structures of this class of compounds and their inhibitory- and antibacterial activities is described here, leading to a set of potent RNA polymerase inhibitors with antibacterial activity. Characterization of this bioactivity, including studies of the mechanism of action, is provided, highlighting the power of the reverse chemical genetics approach in providing tools to inhibit the bacterial RNA polymerase. 相似文献
405.
406.
Dario Fortunati Sjur Reppe Åse-Karine Fjeldheim Marit Nielsen Vigdis T. Gautvik Kaare M. Gautvik 《Matrix biology》2010,29(7):594-601
Periostin is a 90 kDa secreted protein, originally identified in murine osteoblast-like cells, with a distribution restricted to collagen-rich tissues and certain tumors. In this paper, we first analyzed the expression of periostin mRNA and protein in human fetal osteoblasts (hFOB) and human osteosarcoma (hOS) cell lines by RT real-time PCR and Western blot, respectively. The hFOB 1.19 and three hOS (MHM, KPDXM and Eggen) showed highly variable periostin mRNA levels and protein. Second, we showed that the expression of periostin mRNA was inversely related to the cells' abilities to differentiate and mineralize. Then, we investigated the regulation of periostin mRNA in hFOB after siRNA treatment and in mouse primary osteoblasts (mOB) treated with PTH. Knock-down of periostin mRNA, down-regulated PTHrP, but did not affect the expression of other important markers of differentiation such as RUNX2. In addition, periostin mRNA was transiently up-regulated in osteoblasts by PTH. Finally, the localization of periostin and its partially co-localization with collagen 1a1 mRNA and protein was studied in mouse embryos and postnatal pups using in situ hybridization and immunohistochemistry, respectively. In conclusion, the present study provides novel observations related to the expression, distribution and regulation of periostin in bone cells and extracellular matrix. 相似文献
407.
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma of the skin. Although it is 40 times less common than malignant melanoma, its mortality is much higher compared to melanoma. From 1986 to 2001 there was rapidly increasing incidence in reported cases of MCC, with a tripling in the rate over this 15-year period. The vast majority of MCC presents on sun-exposed skin. The head and neck area is the most common site of tumor occurrence. We present 70-year old female patient with painless red-colored nodule, size 2 x 2 x 2 cm on the dorsal side of mid left forearm. The surgical excision with negative margins was performed, and pathohistological analysis confirmed Merkel cell carcinoma. Sentinel lymph node biopsy was negative. In conclusion, as MCC is a very aggressive rare skin carcinoma with lethal outcome, it should be mandatory to perform biopsies of any suspected skin lesion. 相似文献
408.
Vincenza Gorgoglione Dario Domenico Lofrumento Daniela Isabel Abbrescia Nicola Elio Lofrumento 《Archives of biochemistry and biophysics》2010,504(2):210-220
We have investigated whether increase in the oxidation rate of exogenous cytochrome c (cyto-c), induced by long-chain ceramides, might be due to an increased rate of cytosolic NADH/cyto-c electron transport pathway. This process was identified in isolated liver mitochondria and has been studied in our laboratory for many years. Data from highly specific test of sulfite oxidase prove that exogenous cyto-c both in the absence and presence of ceramide cannot permeate through the mitochondrial outer membrane. However, the oxidation of added NADH, mediated by exogenous cyto-c and coupled to the generation of a membrane potential supporting the ATP synthesis, can also be stimulated by ceramide. The results obtained suggest that ceramide molecules, by increasing mitochondrial permeability, with the generation of either raft-like platforms or channels, may have a dual function. They can promote the release of endogenous cyto-c and activate, with an energy conserving process, the oxidation of cytosolic NADH either inducing the formation of new respiratory contact sites or increasing the frequency of the pre-existing porin contact sites. In agreement with the data in the literature, an increase of mitochondrial ceramide molecules level may represent an efficient strategy to activate and support the correct execution of apoptotic program. 相似文献
409.
Fabian Buller Martina Steiner Jörg Scheuermann Luca Mannocci Ina Nissen Manuel Kohler Christian Beisel Dario Neri 《Bioorganic & medicinal chemistry letters》2010,20(14):4188-4192
DNA-encoded chemical libraries are large collections of small organic molecules, individually coupled to DNA fragments that serve as amplifiable identification bar codes. The isolation of specific binders requires a quantitative analysis of the distribution of DNA fragments in the library before and after capture on an immobilized target protein of interest. Here, we show how Illumina sequencing can be applied to the analysis of DNA-encoded chemical libraries, yielding over 10 million DNA sequence tags per flow-lane. The technology can be used in a multiplex format, allowing the encoding and subsequent sequencing of multiple selections in the same experiment. The sequence distributions in DNA-encoded chemical library selections were found to be similar to the ones obtained using 454 technology, thus reinforcing the concept that DNA sequencing is an appropriate avenue for the decoding of library selections. The large number of sequences obtained with the Illumina method now enables the study of very large DNA-encoded chemical libraries (>500,000 compounds) and reduces decoding costs. 相似文献
410.
A recent study sheds new light on the visual cues used by Drosophila to regulate flight altitude. The striking similarity with previously identified steering mechanisms provides a coherent basis for novel models of vision-based flight control in insects and robots. 相似文献