全文获取类型
收费全文 | 3482篇 |
免费 | 224篇 |
国内免费 | 19篇 |
专业分类
化学 | 2654篇 |
晶体学 | 37篇 |
力学 | 51篇 |
数学 | 267篇 |
物理学 | 716篇 |
出版年
2023年 | 14篇 |
2022年 | 68篇 |
2021年 | 80篇 |
2020年 | 66篇 |
2019年 | 73篇 |
2018年 | 50篇 |
2017年 | 49篇 |
2016年 | 142篇 |
2015年 | 107篇 |
2014年 | 155篇 |
2013年 | 222篇 |
2012年 | 285篇 |
2011年 | 302篇 |
2010年 | 180篇 |
2009年 | 166篇 |
2008年 | 225篇 |
2007年 | 219篇 |
2006年 | 178篇 |
2005年 | 167篇 |
2004年 | 186篇 |
2003年 | 126篇 |
2002年 | 140篇 |
2001年 | 61篇 |
2000年 | 81篇 |
1999年 | 40篇 |
1998年 | 22篇 |
1997年 | 17篇 |
1996年 | 28篇 |
1995年 | 27篇 |
1994年 | 17篇 |
1993年 | 20篇 |
1992年 | 38篇 |
1991年 | 21篇 |
1990年 | 7篇 |
1989年 | 10篇 |
1988年 | 7篇 |
1987年 | 10篇 |
1986年 | 8篇 |
1985年 | 17篇 |
1984年 | 7篇 |
1982年 | 6篇 |
1981年 | 11篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 10篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 11篇 |
1973年 | 4篇 |
排序方式: 共有3725条查询结果,搜索用时 15 毫秒
51.
Carbohydrate-protein interactions play important biological roles in living organisms. For the most part, biophysical and biochemical methods have been used for studying these biomolecular interactions. Less attention has been given to the development of high-throughput methods to elucidate recognition events between carbohydrates and proteins. In the current effort to develop a novel high-throughput tool for monitoring carbohydrate-protein interactions, we prepared carbohydrate microarrays by immobilizing maleimide-linked carbohydrates on thiol-derivatized glass slides and carried out lectin binding experiments by using these microarrays. The results showed that carbohydrates with different structural features selectively bound to the corresponding lectins with relative binding affinities that correlated with those obtained from solution-based assays. In addition, binding affinities of lectins to carbohydrates were also quantitatively analyzed by determining IC(50) values of soluble carbohydrates with the carbohydrate microarrays. To fabricate carbohydrate chips that contained more diverse carbohydrate probes, solution-phase parallel and enzymatic glycosylations were performed. Three model disaccharides were in parallel synthesized in solution-phase and used as carbohydrate probes for the fabrication of carbohydrate chips. Three enzymatic glycosylations on glass slides were consecutively performed to generate carbohydrate microarrays that contained the complex oligosaccharide, sialyl Le(x). Overall, these works demonstrated that carbohydrate chips could be efficiently prepared by covalent immobilization of maleimide-linked carbohydrates on the thiol-coated glass slides and applied for the high-throughput analyses of carbohydrate-protein interactions. 相似文献
52.
Yamamoto T Mukai SR Endo A Nakaiwa M Tamon H 《Journal of colloid and interface science》2003,264(2):532-537
Growth of colloidal particles formed during the sol-gel transition of a resorcinol-formaldehyde (RF) solution was simulated based on the population balance equation by using the discrete-sectional model (DSM). During the early stage of the sol-gel transition, the transient change of sizes of colloidal particles estimated by this method agreed well with the previous experimental observation by dynamic light scattering (DLS), which confirmed the influence of the catalyst concentration of a starting RF solution on the growth rate of the particles. From the size distribution of colloidal particles predicted at the gelation time, the surface area of a RF hydrogel after the completion of the sol-gel transition was estimated, which coincided with the BET surface area of a RF aerogel because the porous structure of a hydrogel was maintained and few micropores were formed during supercritical drying. 相似文献
53.
Oxygen is electroreduced to water on a carbon cathode coated with wired bilirubin oxidase in a pH 7.4 0.15 M NaCl phosphate buffer solution at 37 °C at much lesser polarization than it is on a pure platinum cathode in 0.5 M H2SO4. While the wired bilirubin oxidase cathode operates for over a week in the aerated or oxygenated buffer solution, it is degraded rapidly when in serum. We reported earlier that in the presence of O2 an intermediate product of the electrooxidation of urate, which is a normal serum component, irreversibly damages the wired bilirubin oxidase and also reported that the electrocatalyst is irreversibly damaged, in the absence of urate, when it is brought, by disconnecting the electrode, to the O2/H2O half cell potential at pH 7.4. Here we report that a) dissolved bilirubin oxidase is irreversibly and rapidly damaged by urate in the presence of O2; and b) that the immobilized wired bilirubin oxidase electrocatalyst is not only irreversibly deactivated by urate in the presence of O2 in a few hours, but is initially reversibly deactivated, in 1 min or less, by the urate in the presence of O2. 相似文献
54.
Shin Kamijo 《Tetrahedron letters》2006,47(32):5629-5632
Cyclic vinylogous triflate hemiacetals can serve as ‘synthetic equivalents’ for alkynyl aldehydes: treatment of a vinylogous triflate hemiacetal with excess amounts of Grignard reagents produces acyclic alkynyl alcohols in good to high yields. This transformation likely involves the Grob-type C-C bond cleaving fragmentation to form the alkynyl aldehyde in situ. Subsequent nucleophilic attack of the Grignard reagent furnishes secondary alkynols. Vinylogous triflate hemiacetals are easily prepared by DIBALH reduction of vinylogous acyl triflates, which are derived from cyclic 1,3-diketones. 相似文献
55.
This study examined the pharmacokinetic disposition, oral absorption and hepatic extraction of itraconazole and its active metabolite, hydroxyitraconazole, in rats. After i.v. injection, serum itraconazole concentrations decreased biexponentially, with an average terminal elimination half-life, volume of distribution and systemic clearance of 4.9 h, 6.0 l/kg and 14.2 ml/min/kg, respectively. When given orally, its absorption was low, with a mean absolute bioavailability of 16.6%. The metabolite to parent drug area under the curve (AUC) ratio was higher after oral administration compared with i.v. injection (mean ratio, 2.7 vs. 0.9). The hepatic drug extraction ratio determined after femoral and portal vein administration averaged 18.5%. When hydroxyitraconazole was injected i.v., the elimination half-life, volume of distribution and systemic clearance of itraconazole averaged 10.0 h, 2.4 l/kg and 3.4 ml/min/kg, respectively. The fraction of the systemically available itraconazole that was metabolized to hydroxyitraconazole was 21.0% and 76.0% after i.v. and oral administration, respectively. In summary, this study is the first reporting the hepatic extraction of itraconazole and the i.v. disposition characteristics of hydroxyitraconazole in rats. Itraconazole is a drug with a low hepatic extraction ratio and its systemic clearance appears to be largely accounted for by hepatic metabolism. 相似文献
56.
[reaction: see text]. A novel synthetic methodology for 2,5-disubstituted tetrahydrofurans having an allenyl group at the 3-position via Prins-type cyclization was developed. The reaction led to excellent selectivity and moderate to high yields. 相似文献
57.
The detailed reaction dynamics of CH(3)I photodissociation at 304 nm were studied by using high-resolution long time-delayed core-sampling photofragment translation spectroscopy. The vibrational state distributions of the photofragment, i.e., CH(3), are directly resolved due to the high kinetic resolution of this experiment for the first time. CH(3) radicals produced from I((3)Q(0+)), I((1)Q(1) <--( 3)Q(0+)), and I((3)Q(1)) channels are populated in different vibrational state distributions. The I((3)Q(0+)) and I((3)Q(1)) channels show only progressions in the nu2'(a2") umbrella bending mode, and the I((1)Q(1) <-- (3)Q(0+)) channel shows both progression in the nu2' umbrella bending mode and a small amount of excitation in the nu1'(a1') C-H stretching mode. The photodissociation processes from the vibrational hot band of CH(3)I (upsilon3 = 1, upsilon3 = 2) were also detected, primarily because of the absorption probability from the vibrational excited states, i.e., hot bands are relatively enhanced. Photofragments from the hot bands of CH(3)I show a cold vibrational distribution compared to that from the vibrational ground state of CH(3)I. The I* quantum yield and the curve crossing possibility were also studied for the ground vibrational state of CH(3)I. The potential energy at the curve crossing point was calculated to be 32 790 cm(-1) by using the one-dimensional Landau-Zener model. 相似文献
58.
59.
Inchul Shin Ian Davis Karinel Nieves-Merced Yifan Wang Stanton McHardy Aimin Liu 《Chemical science》2021,12(11):3984
SfmD is a heme-dependent enzyme in the biosynthetic pathway of saframycin A. Here, we present a 1.78 Å resolution de novo crystal structure of SfmD, which unveils a novel heme cofactor attached to the protein with an unusual HxnHxxxC motif (n ∼ 38). This heme cofactor is unique in two respects. It contains a single thioether bond in a cysteine–vinyl link with Cys317, and the ferric heme has two axial protein ligands, i.e., His274 and His313. We demonstrated that SfmD heme is catalytically active and can utilize dioxygen and ascorbate for a single-oxygen insertion into 3-methyl-l-tyrosine. Catalytic assays using ascorbate derivatives revealed the functional groups of ascorbate essential to its function as a cosubstrate. Abolishing the thioether linkage through mutation of Cys317 resulted in catalytically inactive SfmD variants. EPR and optical data revealed that the heme center undergoes a substantial conformational change with one axial histidine ligand dissociating from the iron ion in response to substrate 3-methyl-l-tyrosine binding or chemical reduction by a reducing agent, such as the cosubstrate ascorbate. The labile axial ligand was identified as His274 through redox-linked structural determinations. Together, identifying an unusual heme cofactor with a previously unknown heme-binding motif for a monooxygenase activity and the structural similarity of SfmD to the members of the heme-based tryptophan dioxygenase superfamily will broaden understanding of heme chemistry.The de novo crystal structure of SfmD reveals a novel c-type heme cofactor for promoting a monooxygenation reaction in the biosynthetic pathway of saframycin A. 相似文献
60.
K. H. Kim J. H. Lee M. Y. Ko K. S. Shin J. S. Kang W. C. Mar J. R. Youm 《Chromatographia》2002,55(1-2):81-85
Summary A method for the assay of R-(+)- and S-(−)- metoprolol in human urine has been developed using gas chromatography-mass spectrometry.
The method involved purification by liquid-liquid extraction and derivatization with N-methyl-N-(trimethylsilyl)trifluoroacetamide
to form an O-silyl ether, followed by subsequent chiral derivatization with (−)-α-methoxy-α-(trifluoromethyl)phenylacetyl
chloride to form diastereomeric amide. The reaction was rapid and the diastereomeric derivatives were well resolved. Quantitation
was performed by selected-ion monitoring of fragment ions of the diastereomers in electron impact ionization mode. No racemization
was found during the reaction. The detection limit was 0.5 ng·mL−1. The intra-day variation ranged between 0.38 and 7.86% in relation to the measured concentration and inter-day variation
was 2.26–8.06%. The method has been applied to the determination of R-(+)-and S-(−)- metoprolol in human urine from healthy
volunteers dosed with racemic metoprolol tartrate. 相似文献