全文获取类型
收费全文 | 723篇 |
免费 | 16篇 |
国内免费 | 5篇 |
专业分类
化学 | 455篇 |
晶体学 | 2篇 |
力学 | 4篇 |
数学 | 75篇 |
物理学 | 208篇 |
出版年
2022年 | 7篇 |
2021年 | 8篇 |
2020年 | 6篇 |
2019年 | 8篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 19篇 |
2015年 | 9篇 |
2014年 | 19篇 |
2013年 | 35篇 |
2012年 | 49篇 |
2011年 | 58篇 |
2010年 | 28篇 |
2009年 | 20篇 |
2008年 | 44篇 |
2007年 | 48篇 |
2006年 | 32篇 |
2005年 | 43篇 |
2004年 | 40篇 |
2003年 | 40篇 |
2002年 | 29篇 |
2001年 | 12篇 |
2000年 | 23篇 |
1999年 | 19篇 |
1998年 | 13篇 |
1997年 | 6篇 |
1996年 | 11篇 |
1995年 | 8篇 |
1994年 | 10篇 |
1993年 | 9篇 |
1992年 | 19篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 4篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1967年 | 1篇 |
1944年 | 2篇 |
1935年 | 3篇 |
排序方式: 共有744条查询结果,搜索用时 15 毫秒
81.
Tam T. T. N. Nguyen Jesper Østergaard Bente Gammelgaard 《Analytical and bioanalytical chemistry》2015,407(28):8497-8503
82.
Oligonucleotide chemistry has been developed greatly over the past three decades, with many advances in increasing nuclease resistance, enhancing duplex stability and assisting with cellular uptake. Locked nucleic acid (LNA) is a structurally rigid modification that increases the binding affinity of a modified-oligonucleotide. In contrast, unlocked nucleic acid (UNA) is a highly flexible modification, which can be used to modulate duplex characteristics. In this tutorial review, we will compare the synthetic routes to both of these modifications, contrast the structural features, examine the hybridization properties of LNA and UNA modified duplexes, and discuss how they have been applied within biotechnology and drug research. LNA has found widespread use in antisense oligonucleotide technology, where it can stabilize interactions with target RNA and protect from cellular nucleases. The newly emerging field of siRNAs has made use of LNA and, recently, also UNA. These modifications are able to increase double-stranded RNA stability in serum and decrease off-target effects seen with conventional siRNAs. LNA and UNA are also emerging as versatile modifications for aptamers. Their application to known aptamer structures has opened up the possibility of future selection of LNA-modified aptamers. Each of these oligonucleotide technologies has the potential to become a new type of therapy to treat a wide variety of diseases, and LNA and UNA will no doubt play a part in future developments of therapeutic and diagnostic oligonucleotides. 相似文献
83.
Johannsen MW Crispino L Wamberg MC Kalra N Wengel J 《Organic & biomolecular chemistry》2011,9(1):243-252
The synthesis of 2'-amino-LNA (the 2'-amino derivative of locked nucleic acid) has opened up a number of exciting possibilities with respect to modified nucleic acids. While maintaining the excellent duplex stability inferred by LNA-type oligonucleotides, the nitrogen in the 2'-position of 2'-amino-LNA monomers provides an excellent handle for functionalisation. Herein, the synthesis of amino acid functionalised 2'-amino-LNA derivatives is described. Following ON synthesis, a glycyl unit attached to the N2'-position of 2'-amino-LNA monomers was further acylated with a variety of amino acids. On binding to DNA/RNA complements, the modified ONs induce a marked increase in thermal stability, which is particularly apparent in a buffer system with a low salt concentration. The increase in thermal stability is thought to be caused, at least in part, by decreased electrostatic repulsion between the negatively charged phosphate backbones when positively charged amino acid residues are appended. Upon incorporation of more than one 2'-amino-LNA modification, the effects are found to be nearly additive. For comparison, 2'-amino-LNA derivatives modified with uncharged groups have been synthesised and their effect on duplex thermal stability likewise investigated. 相似文献
84.
Peptidoglycan is a widespread bacterial PAMP molecule and a powerful initiator of innate immune responses. It consists of repeating units of MDP, which as a monomer is only weakly immunostimulatory. Here, MDP-coupled dendrimers were prepared and investigated for stimulation of pig blood mononuclear cells. Compared to monomeric MDP, MDP-dendrimers induced a markedly enhanced production of IL-12 p40, IL-1β and IL-6 and completely down-regulated surface expression of B7 and MHC class II. These results suggest a possible novel strategy based on controlled multimerization of minimal PAMP motifs on dendrimers for preparing molecularly defined immunostimulators with predictable bioactivities. 相似文献
85.
Holm R Schönbeck C Askjær S Jensen H Westh P Østergaard J 《Journal of separation science》2011,34(22):3221-3230
The interaction of the bile salts taurocholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate, and glycochenodeoxycholate present in man, dog, and rat with α-cyclodextrin and 2-hydroxypropyl-α-cyclodextrin was investigated by mobility shift affinity capillary electrophoresis. The cyclodextrins are applied as excipients for solubilisation of drug substances with poor aqueous solubility. Accurate determination of stability constants is challenging for weak analyte-ligand interactions such as the conjugated bile salt α-cyclodextrin interactions. A new approach for correction of medium effects due to the high additive concentrations in the background electrolyte was introduced. The use of prostaglandin A(1) as an interacting marker molecule offered a more satisfactory approach for correction than the commonly employed methods based on viscosity or current ratios. The interacting marker was chosen over a non-interacting marker to avoid the difficult validation of the non-interacting properties. The investigated bile salts all interacted with α-cyclodextrin and 2-hydroxypropyl-α-cyclodextrin. Stability constants ranging from 14 to 95 M(-1) were obtained with slightly higher affinities toward the substituted cyclodextrin. Molecular modelling demonstrated that the interaction between the two species involves the side chain of the bile salt. All together, these results indicate minor bile salt-mediated displacement of substances from α-cyclodextrin complexes in the small intestine. 相似文献
86.
87.
Birk T Pedersen KS Piligkos S Thuesen CA Weihe H Bendix J 《Inorganic chemistry》2011,50(12):5312-5314
In the solid state, MnF(salen) forms chains wherein fairly linear fluoride bridges between high-spin Mn(III) centers are observed. We interpret the magnetic properties of these chains by use of the classical Fisher model and by use of the high-temperature expansion approach, as well as by exact matrix diagonalization of the spin Hamiltonian, of model rings. In solution, electron paramagnetic resonance shows the chains to be symmetrically cleaved to monomeric MnF(salen). 相似文献
88.
89.
Ohne Zusammenfassung 相似文献
90.
Lasse Jrgensen Cehofski Anders Kruse Mads Odgaard Mng Benn Falch Sejergaard Anders Schlosser Grith Lykke Sorensen Jakob Grauslund Bent Honor Henrik Vorum 《Molecules (Basel, Switzerland)》2022,27(17)
Central retinal vein occlusion (CRVO) is a visually disabling condition resulting from a thrombus in the major outflow vessel of the eye. The inflammatory response in CRVO is effectively treated with a dexamethasone (DEX) intravitreal implant. Uncovering the proteome changes following DEX implant intervention in CRVO may identify key proteins that mediate the beneficial effects of DEX. In six Göttingen minipigs, CRVO was induced in both eyes with an argon laser using a well-established experimental model. The right eyes were treated with a DEX intravitreal implant (Ozurdex, Allergan), while the left control eyes received a sham injection. Eight weeks after DEX intervention, retinal samples were collected and analyzed with tandem mass tag-based mass spectrometry. DEX implant intervention resulted in the upregulation of peptidyl-prolyl cis–trans isomerase FKBP5 (FKBP5) and ubiquilin-4. Immunohistochemistry showed expression of FKBP5 in the nuclei in all cellular layers of the retina. Cell adhesion molecule 3, tumor necrosis factor receptor superfamily member 16, and trans-1,2-dihydrobenzene-1,2-diol dehydrogenase were downregulated following DEX intervention. The upregulation of the corticosteroid-sensitive protein FKBP5 suggests that the implant remained active at the molecular level after eight weeks of treatment. Future studies may investigate if FKBP5 regulates the efficacy and duration of the DEX implant. 相似文献