全文获取类型
收费全文 | 444篇 |
免费 | 16篇 |
国内免费 | 4篇 |
专业分类
化学 | 309篇 |
力学 | 3篇 |
数学 | 57篇 |
物理学 | 95篇 |
出版年
2022年 | 4篇 |
2021年 | 7篇 |
2020年 | 6篇 |
2019年 | 7篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 15篇 |
2015年 | 6篇 |
2014年 | 16篇 |
2013年 | 26篇 |
2012年 | 40篇 |
2011年 | 43篇 |
2010年 | 22篇 |
2009年 | 11篇 |
2008年 | 30篇 |
2007年 | 30篇 |
2006年 | 26篇 |
2005年 | 24篇 |
2004年 | 29篇 |
2003年 | 27篇 |
2002年 | 25篇 |
2001年 | 11篇 |
2000年 | 9篇 |
1999年 | 11篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有464条查询结果,搜索用时 390 毫秒
51.
Click Chemistry Mediated Functionalization of Vertical Nanowires for Biological Applications 下载免费PDF全文
Surendra Vutti Dr. Sanne Schoffelen Dr. Jessica Bolinsson Nina Buch‐Månson Prof. Nicolas Bovet Prof. Jesper Nygård Prof. Karen L. Martinez Prof. Morten Meldal 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(2):496-500
Semiconductor nanowires (NWs) are gaining significant importance in various biological applications, such as biosensing and drug delivery. Efficient and controlled immobilization of biomolecules on the NW surface is crucial for many of these applications. Here, we present for the first time the use of the CuI‐catalyzed alkyne–azide cycloaddition and its strain‐promoted variant for the covalent functionalization of vertical NWs with peptides and proteins. The potential of the approach was demonstrated in two complementary applications of measuring enzyme activity and protein binding, which is of general interest for biological studies. The attachment of a peptide substrate provided NW arrays for the detection of protease activity. In addition, green fluorescent protein was immobilized in a site‐specific manner and recognized by antibody binding to demonstrate the proof‐of‐concept for the use of covalently modified NWs for diagnostic purposes using minute amounts of material. 相似文献
52.
Mathias B. Danielsen Dr. Chenguang Lou Jolanta Lisowiec-Wachnicka Prof. Anna Pasternak Per T. Jørgensen Prof. Jesper Wengel 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(6):1368-1379
Off-target effects remain a significant challenge in the therapeutic use of gapmer antisense oligonucleotides (AONs). Over the years various modifications have been synthesized and incorporated into AONs, however, precise control of RNase H-induced cleavage and target sequence selectivity has yet to be realized. Herein, the synthesis of the uracil and cytosine derivatives of a novel class of 2′-deoxy-2′-fluoro-3′-C-hydroxymethyl-β-d -lyxo-configured nucleotides has been accomplished and the target molecules have been incorporated into AONs. Experiments on exonuclease degradation showed improved nucleolytic stability relative to the unmodified control. Upon the introduction of one or two of the novel 2′-fluoro-3′-C-hydroxymethyl nucleotides as modifications in the gap region of a gapmer AON was associated with efficient RNase H-mediated cleavage of the RNA strand of the corresponding AON:RNA duplex. Notably, a tailored single cleavage event could be engineered depending on the positioning of a single modification. The effect of single mismatched base pairs was scanned along the full gap region demonstrating that the modification enables a remarkable specificity of RNase H cleavage. A cell-based model system was used to demonstrate the potential of gapmer AONs containing the novel modification to mediate gene silencing. 相似文献
53.
54.
A CE procedure was established for the nondenaturing separation and identification of the isoforms of the actin-binding human plasma protein Gc-globulin. To characterize interactions with globular actin (G-actin), a novel method was developed for the simultaneous qualitative assessment of the binding interaction between the three major isoforms of Gc-globulin and G-actin using pre-equilibrium affinity CE and UV detection. Evidence was found that some difference in binding affinity existed among the isoforms, although the quantification of this difference was not feasible by UV detection because of the high affinity nature of the binding. The difference in affinity appeared to be related to the pI of the isoforms; a high pI corresponding to a high affinity. For quantitative binding studies Gc-globulin was fluorescently labeled with 5-(and-6)-carboxyfluorescein, succinimidyl ester (CFSE). Data suggested that extensive labeling interfered with actin binding but with moderately labeled Gc-globulin it was possible to determine a dissociation constant of K(d) = 21 +/- 1 nM for the binding between labeled Gc-globulin and G-actin using pre-equilibrium affinity CE and LIF detection. 相似文献
55.
Tholander F Muroya A Roques BP Fournié-Zaluski MC Thunnissen MM Haeggström JZ 《Chemistry & biology》2008,15(9):920-929
M1 aminopeptidases comprise a large family of biologically important zinc enzymes. We show that peptide turnover by the M1 prototype, leukotriene A4 hydrolase/aminopeptidase, involves a shift in substrate position associated with exchange of zinc coordinating groups, while maintaining the overall coordination geometry. The transition state is stabilized by residues conserved among M1 members and in the final reaction step, Glu-296 of the canonical zinc binding HEXXH motif shuffles a proton from the hydrolytic water to the leaving group. Tripeptide substrates bind along the conserved GXMEN motif, precisely occupying the distance between Glu-271 and Arg-563, whereas the Arg specificity is governed by a narrow S1 pocket capped with Asp-375. Our data provide detailed insights to the active site chemistry of M1 aminopeptidases and will aid in the development of novel enzyme inhibitors. 相似文献
56.
Astakhova IV Korshun VA Wengel J 《Chemistry (Weinheim an der Bergstrasse, Germany)》2008,14(35):11010-11026
In recent years, fluorescently labeled oligonucleotides have become a widely used tool in diagnostics, DNA sequencing, and nanotechnology. The recently developed (phenylethynyl)pyrenes are attractive dyes for nucleic acid labeling, with the advantages of long-wave emission relative to the parent pyrene, high fluorescence quantum yields, and the ability to form excimers. Herein, the synthesis of six (phenylethynyl)pyrene-functionalized locked nucleic acid (LNA) monomers M(1)-M(6) and their incorporation into DNA oligomers is described. Multilabeled duplexes display higher thermal stabilities than singly modified analogues. An increase in the number of phenylethynyl substituents attached to the pyrene results in decreased binding affinity towards complementary DNA and RNA and remarkable bathochromic shifts of absorption/emission maxima relative to the parent pyrene fluorochrome. This bathochromic shift leads to the bright fluorescence colors of the probes, which differ drastically from the blue emission of unsubstituted pyrene. The formation of intra- and interstrand excimers was observed for duplexes that have monomers M(1)-M(6) in both complementary strands and in numerous single-stranded probes. If more phenylethynyl groups are inserted, the detected excimer signals become more intense. In addition, (phenylethynyl)pyrenecarbonyl-LNA monomers M(4), M(5), and M(6) proved highly useful for the detection of single mismatches in DNA/RNA targets. 相似文献
57.
Desnous C Babu BR Moriou C Mayo JU Favre A Wengel J Clivio P 《Journal of the American Chemical Society》2008,130(1):30-31
The LNA dinucleotide mimic of TpT whose two-sugar puckers are locked in the C3'-endo conformation selectively produces the corresponding cyclobutane pyrimidine dimer under 254 nm irradiation. In the natural series (TpT) the sugar puckers are in a major C2'-endo sugar conformation and the (6-4) photoproduct is also produced. Consequently, this study demonstrates that the C2'-endo conformation of the sugar pucker is necessary for (6-4) photoproduct formation. 相似文献
58.
Lidija Posavec Jesper T. N. Knijnenburg Florentine M. Hilty Frank Krumeich Sotiris E. Pratsinis Michael B. Zimmermann 《Journal of nanoparticle research》2016,18(10):310
Rapid calcium (Ca) dissolution from nanostructured Ca phosphate and carbonate (CaCO3) powders may allow them to be absorbed in much higher fraction in humans. Nanosized Ca phosphate and CaCO3 made by flame-assisted spray pyrolysis were characterized by nitrogen adsorption, X-ray diffraction (XRD), Raman spectroscopy, and transmission electron microscopy. As-prepared nanopowders contained both CaCO3 and CaO, but storing them under ambient conditions over 130 days resulted in a complete transformation into CaCO3, with an increase in both crystal and particle sizes. The small particle size could be stabilized against such aging by cation (Mg, Zn, Sr) and anion (P) doping, with P and Mg being most effective. Calcium phosphate nanopowders made at Ca:P ≤ 1.5 were XRD amorphous and contained γ-Ca2P2O7 with increasing hydroxyapatite content at higher Ca:P. Aging of powders with Ca:P = 1.0 and 1.5 for over 500 days gradually increased particle size (but less than for CaCO3) without a change in phase composition or crystallinity. In 0.01 M H3PO4 calcium phosphate nanopowders dissolved ≈4 times more Ca than micronsized compounds and about twice more Ca than CaCO3 nanopowders, confirming that nanosizing and/or amorphous structuring sharply increases Ca powder dissolution. Because higher Ca solubility in vitro generally leads to greater absorption in vivo, these novel FASP-made Ca nanostructured compounds may prove useful for nutrition applications, including supplementation and/or food fortification. 相似文献
59.
Jesper Koning Joseph O. Indekeu 《The European Physical Journal B - Condensed Matter and Complex Systems》2016,89(11):248
It is known that an engine with ideal efficiency (η = 1 for a chemical engineand e =eCarnot for a thermal one) has zero powerbecause a reversible cycle takes an infinite time. However, at least from a theoreticalpoint of view, it is possible to conceive (irreversible) engines with nonzero power thatcan reach ideal efficiency. Here this is achieved by replacing the usual linear transportlaw by a sublinear one and taking the step-function limit for the particle current(chemical engine) or heat current (thermal engine) versus the applied force. It is shownthat in taking this limit exact thermodynamic inequalities relating the currents to theentropy production are not violated. 相似文献
60.
Pernille Tofteng A Hansen TH Brask J Nielsen J Thulstrup PW Jensen KJ 《Organic & biomolecular chemistry》2007,5(14):2225-2233
De novo design and total chemical synthesis of proteins provides a powerful approach for biological and biophysical studies with the ability to prepare artificial proteins with tailored properties, potentially of importance for biophysical studies, material science, nanobioscience, and as molecular probes. In this paper, the previously developed concept of carbohydrates as templates is employed in the de novo design of model proteins (artificial helix bundles) termed 'carboproteins'. The 4-alpha-helix bundle is a macromolecular structure, where four amphiphilic alpha-helical peptide strands form a hydrophobic core. Here this structure is modified towards achieving metal ion-binding and catalytic activity. We report: (i) test of directional effects from different tetravalent carbohydrate templates, (ii) synthesis and evaluation of carboproteins functionalized with phenol, pyridyl or imidazolyl moieties as potential ligands for metal ion-binding as well as for catalysis. Our results include: (i) support of our previous 'controversial' finding that for some carboproteins the degree of alpha-helicity depends on the template, i.e., that there is, to some extent, a controlling effect from the template, (ii) demonstration of binding of Cu(ii) to tetra-functional carboproteins by electrospray ionization-time of flight-mass spectrometry (ESI-TOF-MS), UV-VIS absorption spectroscopy and size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS); (iii) a kinetic investigation of the esterase activity. 相似文献