全文获取类型
收费全文 | 102909篇 |
免费 | 1343篇 |
国内免费 | 518篇 |
专业分类
化学 | 42483篇 |
晶体学 | 988篇 |
力学 | 7157篇 |
数学 | 34953篇 |
物理学 | 19189篇 |
出版年
2023年 | 184篇 |
2022年 | 269篇 |
2021年 | 364篇 |
2020年 | 492篇 |
2019年 | 478篇 |
2018年 | 10651篇 |
2017年 | 10434篇 |
2016年 | 6750篇 |
2015年 | 1449篇 |
2014年 | 1026篇 |
2013年 | 1522篇 |
2012年 | 5340篇 |
2011年 | 12140篇 |
2010年 | 6590篇 |
2009年 | 6837篇 |
2008年 | 7996篇 |
2007年 | 10048篇 |
2006年 | 1598篇 |
2005年 | 2574篇 |
2004年 | 2638篇 |
2003年 | 2799篇 |
2002年 | 1898篇 |
2001年 | 678篇 |
2000年 | 655篇 |
1999年 | 519篇 |
1998年 | 554篇 |
1997年 | 489篇 |
1996年 | 544篇 |
1995年 | 409篇 |
1994年 | 395篇 |
1993年 | 395篇 |
1992年 | 317篇 |
1991年 | 260篇 |
1990年 | 272篇 |
1989年 | 246篇 |
1988年 | 258篇 |
1987年 | 235篇 |
1986年 | 221篇 |
1985年 | 321篇 |
1984年 | 302篇 |
1983年 | 220篇 |
1982年 | 242篇 |
1981年 | 225篇 |
1980年 | 228篇 |
1979年 | 209篇 |
1978年 | 231篇 |
1977年 | 199篇 |
1976年 | 155篇 |
1974年 | 169篇 |
1973年 | 149篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
The goal of the present study is to test the hypothesis that LPA induces proliferation of astrocytes in hippocampus in vivo via phosphorylation of ERK 1/2. We first characterized the expression of GFAP, a special marker fiber protein of astrocytes,
in brain slices after direct injection of LPA into hippocampus by immunohistochemistry, and found that LPA induced a remarkable
proliferation of astrocytes. Then double-lablled immunofluorescence was used to detect GFAP and phosphorylation ERK 1/2 (p-ERK
1/2), LPA induced an immediate (10 min) and transient (<30 min) phosphorylation of ERK 1/2, and sequence sustained activation
of ERK 1/2 was observed, which last for at least 3 weeks after injection of LPA. Reactions are inhibited by U0126, a specific
pharmacological mitogen-activated protein kinase (MEK) inhibitor. Laser confocal scanning was used to study spatial relationship
of p-ERK and astrocytes. Amazingly, the early (<7 days) phosphorylation of ERK 1/2 is not expressed in astrocytes but in area
where neurons and/or in other cell type(s) occupied, expression of p-ERK 1/2 in astrocytes is not detected until 14 days after
LPA injection and lasts for at least 3 weeks. Taken together, these data suggest that LPA play an important role in proliferation
of astrocytes through phosphorylation of ERK 1/2 in hippocampus. It provides further proof for the functions of LPA in CNS
injury, and may contribute to clinical therapy for relative diseases. 相似文献
992.
Samuel K Yin W Stearns RA Tang YS Chaudhary AG Jewell JP Lanza T Lin LS Hagmann WK Evans DC Kumar S 《Journal of mass spectrometry : JMS》2003,38(2):211-221
Metabolic activation of drug candidates to electrophilic reactive metabolites that can covalently modify cellular macromolecules may result in acute and/or idiosyncratic immune system-mediated toxicities in humans. This presents a significant potential liability for the future development of these compounds as safe therapeutic agents. We present here an example of an approach where sites of metabolic activation within a new drug candidate series were rapidly identified using online liquid chromatography/multi-stage mass spectrometry on an ion trap mass spectrometer. This was accomplished by trapping the reactive intermediates formed upon incubation of compounds with rat and human liver microsomes as their corresponding glutathione conjugates and mass spectral characterization of these thiol adducts. Based on the structures of the GSH adducts identified, potential sites and mechanisms of bioactivation within the chemical structure were proposed. These metabolism studies were interfaced with iterative structural modifications of the chemical series in order to block these bioactivation sites within the molecule. This strategy led to a significant reduction in the propensity of the compounds to undergo metabolic activation as evidenced by reductions in the irreversible binding of radioactivity to liver microsomal material upon incubation of tritium-labeled compounds with this in vitro system. With the efficiency and throughput achievable with such an approach, it appears feasible to identify and address the metabolic activation potential of new drug leads during routine metabolite identification studies in an early drug discovery setting. 相似文献
993.
Rudin M Mueggler T Allegrini PR Baumann D Rausch M 《Analytical and bioanalytical chemistry》2003,377(6):973-981
Modern drug development requires technologies that allow rapid translation from the preclinical to the clinical stage. It is obvious that non-invasive imaging modalities such as magnetic resonance imaging (MRI) will play a central role in this regard. This article reviews the use of structural and functional MRI readouts for characterization of central nervous system (CNS) disorders and evaluation of the efficacy of potential CNS drugs. Examples comprise dementia of Alzheimer's type, cerebral ischemia, and neuroinflammation covering both clinical and preclinical aspects. In these examples MRI has been used to obtain relevant structural information on brain atrophy, on the location and extent of ischemic brain areas, and on the number and distribution of demyelinated plaques. These structural data are complemented by readouts assessing the functional consequences associated with the pathomorphological changes. In the last decade, MRI has evolved into a standard tool for the development of CNS drugs. With regard to target-specific/molecular imaging applications MRI is limited by its inherently low sensitivity; complementary imaging modalities utilizing optical and radionuclear reporter systems will thus be required. 相似文献
994.
During attempts to synthesize rare‐earth nitride tellurides black and bead‐shaped single crystals of the title compound sodium praseodymium(III) ditelluride (NaPrTe2) were obtained as a by‐product by reacting a mixture of praseodymium, sodium azide (NaN3) and tellurium at 900 °C for seven days in evacuated torch‐sealed silica vessels. NaPrTe2 crystallizes cubic (space group: Fd3¯m, Z = 16; a = 1285.51(9) pm, Vm = 79.96(1) cm3/mol, R1 = 0.028 for 146 unique reflections) and exhibits the Na+ and Pr3+ cations in slightly distorted octahedra of six telluride anions (d(Na—Te) = 325 pm, d(Pr—Te) = 317 pm) each. The main characteristics of this new structure type for alkali‐metal rare‐earth(III) dichalcogenides can be derived from the rock‐salt type structure (NaCl, cubic closest‐packed Te2— arrangement, all octahedral voids occupied with Na+ and Pr3+) with alternating layers consisting of Na+ and Pr3+ cations in a ratio of 3:1 and 1:3, respectively, piled along the [111] direction. 相似文献
995.
A high-performance capillary electrophoretic (CE) method with electrochemical detection (ED) has been developed for determination of the pharmacologically active flavonoids in Ginkgo biloba L. and phytopharmaceuticals containing its extract. Epicatechin, catechin, rutin, apigenin, luteolin, and quercetin are important flavonoids in this plant. Operated in a wall-jet configuration, a 300 micro m diameter carbon-disk electrode was used as working electrode with good response to the six analytes at +1000 mV (relative to the SCE). Under the optimum conditions, the analytes were separated within 22 min in a borax buffer (pH 9.0). Excellent linearity was obtained over two orders of magnitude and detection limits (S/N=3) ranged from 1.4 x 10(-7) to 5.0 x 10(-7) g mL(-1) for all six analytes. The method was successfully used for assay of Ginkgo biloba L. and its phytopharmaceuticals after a relatively simple extraction procedure; the results obtained were satisfactory. 相似文献
996.
The photoelectron spectrum of tetrakis (methylidene)cyclobutane ( 1 , ‘[4]radialene’) is reported. The electronic states of 1 + are assigned on the basis of model calculations and with reference to related systems. Jahn-Teller activity in the degenerate states is discussed. A failure of the simple LCBO-model for the π(eg)-orbital of 1 is noted and traced to the fact that this orbital, though having a symmetry-equivalent π*-counterpart, does not interact with it. This feature is confined to [4n]radialenes; their total π-energies are therefore higher than those of the other members. It is shown that radialenes, in principle, do not constitute a class analogous to that of the linear polyenes as inferred earlier. 相似文献
997.
The most prominent ion in the mass spectra of C6F5CH2X (X ? H, Br, CH:CH2, COCl, and CH2C6F5) is C7F5H2+, formulated as the pentafluorotropylium cation. This ion is also found, in an amount comparable to the parent ion, in the spectrum of (C6F5)2CH2. The heptafluorotropylium cation is found similarly in the spectrum of C6F5CF3. The mass spectra of (C6F5)2CHBr and [(C6H5)2CH]2 exhibit an ion C13F10H+ as the base peak, which is probably a pentafluorophenylpentafluorotropylium cation. The alcohol (C6F5)2CHOH shows loss of C6F5, followed by 2H, as a major breakdown pathway. The mode of formation, and the subsequent fragmentation, of the major ions in these spectra, are discussed. 相似文献
998.
Ionizable residues play important roles in protein structure and activity, and proton binding is a valuable reporter of electrostatic interactions in these systems. We use molecular dynamics free energy simulations (MDFE) to compute proton pKa shifts, relative to a model compound in solution, for three aspartate side chains in two proteins. Simulations with explicit solvent and with an implicit, dielectric continuum solvent are reported. The implicit solvent simulations use the generalized Born (GB) model, which provides an approximate, analytical solution to Poisson's equation. With explicit solvent, the direction of the pKa shifts is correct in all three cases with one force field (AMBER) and in two out of three cases with another (CHARMM). For two aspartates, the dielectric response to ionization is found to be linear, even though the separate protein and solvent responses can be nonlinear. For thioredoxin Asp26, nonlinearity arises from the presence of two substates that correspond to the two possible orientations of the protonated carboxylate. For this side chain, which is partly buried and has a large pKa upshift, very long simulations are needed to correctly sample several slow degrees of freedom that reorganize in response to the ionization. Thus, nearby Lys57 rotates to form a salt bridge and becomes buried, while three waters intercalate along the opposite edge of Asp26. Such strong and anisotropic reorganization is very difficult to predict with Poisson-Boltzmann methods that only consider electrostatic interactions and employ a single protein structure. In contrast, MDFE with a GB dielectric continuum solvent, used for the first time for pKa calculations, can describe protein reorganization accurately and gives encouraging agreement with experiment and with the explicit solvent simulations. 相似文献
999.
Robert Weis Reto Brun Robert Saf Werner Seebacher 《Monatshefte für Chemie / Chemical Monthly》2003,134(7):1019-1026
Summary. 4-Aminobicyclo[2.2.2]octanones which were prepared in one-pot-reactions from benzylidene acetone and dialkylammonium rhodanides
were reduced stereoselectively to their corresponding alcohols. The activities of the bicyclic compounds against causative
organisms of tropical deseases were examined. The 4-aminobicyclo[2.2.2]octan-2-ols were in general more active against Trypanosoma b. rhodesiense and Plasmodium falciparum than the corresponding keto compounds.
Corresponding author. E-mail: robert.weis@uni-graz.at
Received November 27, 2002; accepted December 2, 2002
Published online May 2, 2003 相似文献
1000.
WO3 and WO3:P (5 mol% H3PO4) thin films were prepared using the sol-gel route and the electrochromic properties of the films were investigated using
in situ spectroelectrochemical methods. The measurements were performed in propylene carbonate solution with 0.1 M LiClO4 as electrolyte. During the cathodic polarization at –0.8 V a blue coloration is observed with a reversible variation between
14% and 84% of the transmittance at λ=633 nm. The kinetics for the bleaching process is faster for the WO3:P film than for the undoped WO3 film.
Electronic Publication 相似文献