全文获取类型
收费全文 | 8785篇 |
免费 | 203篇 |
国内免费 | 11篇 |
专业分类
化学 | 5169篇 |
晶体学 | 122篇 |
力学 | 126篇 |
数学 | 1391篇 |
物理学 | 2191篇 |
出版年
2022年 | 61篇 |
2021年 | 92篇 |
2020年 | 120篇 |
2019年 | 133篇 |
2018年 | 155篇 |
2017年 | 159篇 |
2016年 | 248篇 |
2015年 | 236篇 |
2014年 | 257篇 |
2013年 | 531篇 |
2012年 | 399篇 |
2011年 | 474篇 |
2010年 | 356篇 |
2009年 | 310篇 |
2008年 | 387篇 |
2007年 | 309篇 |
2006年 | 343篇 |
2005年 | 253篇 |
2004年 | 245篇 |
2003年 | 191篇 |
2002年 | 209篇 |
2001年 | 147篇 |
2000年 | 149篇 |
1999年 | 162篇 |
1998年 | 117篇 |
1997年 | 97篇 |
1996年 | 140篇 |
1995年 | 108篇 |
1994年 | 116篇 |
1993年 | 111篇 |
1992年 | 100篇 |
1991年 | 83篇 |
1990年 | 94篇 |
1989年 | 71篇 |
1988年 | 67篇 |
1986年 | 57篇 |
1985年 | 89篇 |
1984年 | 93篇 |
1983年 | 78篇 |
1982年 | 92篇 |
1981年 | 78篇 |
1980年 | 72篇 |
1979年 | 74篇 |
1978年 | 79篇 |
1977年 | 83篇 |
1976年 | 98篇 |
1975年 | 79篇 |
1974年 | 64篇 |
1973年 | 61篇 |
1972年 | 56篇 |
排序方式: 共有8999条查询结果,搜索用时 625 毫秒
991.
Albrow VE Ponder EL Fasci D Békés M Deu E Salvesen GS Bogyo M 《Chemistry & biology》2011,18(6):722-732
Sentrin specific proteases (SENPs) are responsible for activating and deconjugating SUMO (Small Ubiquitin like MOdifier) from target proteins. It remains difficult to study this posttranslational modification due to the lack of reagents that can be used to block the removal of SUMO from substrates. Here, we describe the identification of small molecule SENP inhibitors and active site probes containing aza-epoxide and acyloxymethyl ketone (AOMK) reactive groups. Both classes of compounds are effective inhibitors of hSENPs 1, 2, 5, and 7 while only the AOMKs efficiently inhibit hSENP6. Unlike previous reported peptide vinyl sulfones, these compounds covalently labeled the active site cysteine of multiple recombinantly expressed SENP proteases and the AOMK probe showed selective labeling of these SENPs when added to complex protein mixtures. The AOMK compound therefore represents promising new reagents to study the process of SUMO deconjugation. 相似文献
992.
Structures of tert-butylcarbamate ions in the gas-phase and methanol solution were studied for simple secondary and tertiary carbamates as well as for carbamate-containing products and internal standards for lysosomal enzyme assays used in newborn screening of a α-galactosidase A deficiency (Fabry disease), mucopolysaccharidosis I (Hurler disease), and mucopolysaccharidosis II (Hunter disease). The protonation of simple t-butylcarbamates can occur at the carbonyl group, which is the preferred site in the gas phase. Protonation in methanol solution is more favorable if occurring at the carbamate nitrogen atom. The protonation of more complex t-butylcarbamates occurs at amide and carbamate carbonyl groups, and the ions are stabilized by intramolecular hydrogen bonding, which is affected by solvation. Tertiary carbamates containing aminophenol amide groups were calculated to have substantially greater gas-phase basicities than secondary carbamates containing coumarin amide groups. The main diagnostically important ion dissociation by elimination of 2-methylpropene (isobutylene, i-C(4)H(8)) and carbon dioxide is shown by experiment and theory to proceed in two steps. Energy-resolved collision-induced dissociation of the Hurler's disease enzymatic product ion, which is a coumarin-diamine linker-t-butylcarbamate conjugate (3a(+)), indicated separate energy thresholds for the loss of i-C(4)H(8) and CO(2). Computational investigation of the potential energy surface along two presumed reaction pathways indicated kinetic preference for the migration of a t-butyl hydrogen atom to the carbamate carbonyl resulting in the isobutylene loss. The consequent loss of CO(2) required further proton migrations that had to overcome energy barriers. 相似文献
993.
Kádár Z Kovács D Frank É Schneider G Huber J Zupkó I Bartók T Wölfling J 《Molecules (Basel, Switzerland)》2011,16(6):4786-4806
A straightforward and reliable method for the regioselective synthesis of steroidal 1,4-disubstituted triazoles and 1,5-disubstituted tetrazoles via copper(I)-catalyzed cycloadditions is reported. Heterocycle moieties were efficiently introduced onto the starting azide compound 3β-acetoxy-16β-azidomethylandrost-5-en-17β-ol through use of the "click" chemistry approach. The antiproliferative activities of the newly-synthesized triazoles were determined in vitro on three human gynecological cell lines (HeLa, MCF7 and A2780) using the microculture tetrazolium assay. 相似文献
994.
Agopcan S Çelebi-Ölçüm N Üçışık MN Sanyal A Aviyente V 《Organic & biomolecular chemistry》2011,9(23):8079-8088
In this study, the origins of diastereoselectivity in the hydrogen bonding assisted Diels-Alder reactions of chiral dienes with achiral dienophiles have been investigated with density functional methods. The distortion/interaction model has been applied to shed light on the origins of selectivity. C9-Substituted chiral anthracene templates (R = (CH(3))(OCH(3))(H), R = (CH(3))(OH)(H), R = (CH(3))(CH(2)CH(3))(H) and R = (-CH(2)-C(CH(3))(OCH(3))(H)) are used to rationalize the role of a stereogenic center and H-bonding on the product distribution ratio. Even though hydrogen bonding increases the reactivity of the diene, the stereoselectivity is reduced because of the hydrogen bonding capacity of both diastereomeric transition states. The interaction energies of the studied anthracene templates with N-methyl maleimide at the transition state correlate linearly with an increase in reactivity. The selectivity is determined by both favorable distortion and interaction energies. The π-facial selectivity induced by the presence of a chiral auxiliary in 1-substituted 1,3-pentadienes (R1 = (CH(3))(OCH(3))(H) and R1 = (CH(3))(OH)(H)) has also been modeled in order to rationalize the role of the stereogenic center and H-bonding on the stereoselectivity of an aliphatic diene. In both parts, the product distribution ratios calculated from Boltzmann distributions based on Gibbs free energies are in reasonable agreement with the experimental results. Finally the role of OH-substituted five-membered pyrrolidine on C9 of anthracene is investigated since the successful usage of the conformationally rigid pyrrolidines in asymmetric synthesis is well known. Overall, both in the acyclic system and in anthracene, the facilitation due to H-bonding is reflected in the interaction energies: the higher the difference in interaction energies in the transition structures of the two diastereomers, the more selective the H-bonding assisted Diels-Alder reaction is. 相似文献
995.
Horáková P Macíčková-Cahová H Pivoňková H Spaček J Havran L Hocek M Fojta M 《Organic & biomolecular chemistry》2011,9(5):1366-1371
A simple approach to DNA tail-labelling using terminal deoxynucleotidyl transferase and modified deoxynucleoside triphosphates is presented. Amino- and nitrophenyl-modified dNTPs were found to be good substrates for this enzyme giving 3'-end stretches of different lengths depending on the nucleotide and concentration. 3-Nitrophenyl-7-deazaG was selected as the most useful label because its dNTP was efficiently incorporated by the transferase to form long tail-labels at any oligonucleotide. Accumulation of many nitrophenyl tags per oligonucleotide resulted in a considerable enhancement of voltammetric signals due to the nitro group reduction, thus improving the sensitivity of electrochemical detection of the tail-labelled probes. We demonstrate a perfect discrimination between complementary and non-complementary target DNAs sequences by tail-labelled hybridization probes as well as the ability of tumour suppressor p53 protein to recognize a specific binding site within tail-labelled DNA substrates, making the methodology useful in electrochemical DNA hybridization and DNA-protein interaction assays. 相似文献
996.
Kádár Z Baji Á Zupkó I Bartók T Wölfling J Frank É 《Organic & biomolecular chemistry》2011,9(23):8051-8057
Stereoselective 1,4-Michael addition of azoimide to 17β-acetoxy-5α-adrost-1-en-3-one was carried out to furnish a 1α-azido-3-ketone, which was reduced to give the 3β- and 3α-hydroxy epimers in a ratio of 5 : 2. The Cu(I)-catalyzed 1,3-dipolar cycloaddition of the major isomer to terminal alkynes afforded 1α-triazolyl derivatives, which were deacetylated to the corresponding 3β,17β-diols or oxidized to the analogous 3-ketones. However, the ability of the minor 1α,3α-azidoalcohol to undergo similar cyclization was found to be affected significantly by the steric bulk of the substituents on the alkyne reaction partner. All triazolyl compounds were tested in vitro on three malignant gynecological cell lines (HeLa, MCF7 and A2780). 相似文献
997.
Miskolczy Z Megyesi M Tárkányi G Mizsei R Biczók L 《Organic & biomolecular chemistry》2011,9(4):1061-1070
The inclusion of sanguinarine, a biologically active natural benzophenanthridine alkaloid, in cucurbit[7]uril (CB7) was studied by NMR and ground-state absorption spectroscopy, as well as steady-state and time-resolved fluorescence measurements in aqueous solution. The iminium form of sanguinarine (SA(+)) produces very stable 1 : 1 inclusion complex with CB7 (K = 1.0 × 10(6) M(-1)), whereas the equilibrium constant for the binding of the second CB7 is about 3 orders of magnitude smaller. Marked fluorescence quantum yield and fluorescence lifetime enhancements are found upon encapsulation of SA(+) due to the deceleration of the radiationless deactivation from the single-excited state, but the fluorescent properties of 1 : 1 and 1 : 2 complexes barely differ. The equilibrium between the iminium and alkanolamine forms is shifted 3.69 pK unit upon addition of CB7 as a consequence of the preferential encapsulation of the iminium form and the protection of the 6 position of sanguinarine against the nucleophilic attack by hydroxide anion. On the basis of thermodynamic cycle, about 225 M(-1) is estimated for the equilibrium constant of the complexation between the alkanolamine form of sanguinarine (SAOH) and CB7. The confinement in the CB7 macrocycle can be used to impede the nucleophilic addition of OH(-) to SA(+) and to hinder the photooxidation of SAOH. 相似文献
998.
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
999.
A new simple ultra-high-performance liquid chromatography method with diode array detection (UHPLC-DAD) was developed for
chemical fingerprinting analysis of extracellular metabolites in fermentation broth of Geosmithia spp. The SPE method employing Oasis MCX strong cation-exchange mixed-mode polymeric sorbent was chosen for extraction of
the metabolites. The analyses were performed on an Acquity UPLC BEH C18 column (100 × 2.1 mm i.d.; particle size, 1.7 μm;
Waters) using a gradient elution program with an aqueous solution of trifluoroacetic acid and acetonitrile as the mobile phase.
The applicability of the method was proved by analysis of 38 strains produced by different species and isolated from different
sources (hosts). The results revealed the correlation of obtained UHPLC-DAD fingerprints with taxonomical identity. 相似文献
1000.
Lišková M Voráčová I Klepárník K Hezinová V Přikryl J Foret F 《Analytical and bioanalytical chemistry》2011,400(2):369-379
A number of biologically important molecules, such as DNA, proteins, and antibodies, are routinely conjugated with fluorescent
tags for high-sensitivity analyses. Here, the application of quantum dots in the place of bright and size-tunable luminophores
is studied. Several selected bioconjugation reactions via zero-length cross-linkers, long-chain linkers, and oriented methods
for linking of quantum dots with proteins were tested. Anti-ovalbumin, anti-proliferating cell nuclear antigen, anti-hemagglutinin,
and anti-CD3 membrane protein as model antibodies and annexin V were used as high-specificity selectors. The reaction yield
and efficiency of the prepared immunoluminescent probes were tested by capillary zone electrophoresis with laser-induced fluorescence
detection. 相似文献