全文获取类型
收费全文 | 1494篇 |
免费 | 34篇 |
国内免费 | 9篇 |
专业分类
化学 | 878篇 |
晶体学 | 6篇 |
力学 | 84篇 |
数学 | 241篇 |
物理学 | 328篇 |
出版年
2024年 | 2篇 |
2023年 | 12篇 |
2022年 | 39篇 |
2021年 | 39篇 |
2020年 | 30篇 |
2019年 | 42篇 |
2018年 | 34篇 |
2017年 | 33篇 |
2016年 | 64篇 |
2015年 | 48篇 |
2014年 | 63篇 |
2013年 | 95篇 |
2012年 | 92篇 |
2011年 | 123篇 |
2010年 | 86篇 |
2009年 | 85篇 |
2008年 | 105篇 |
2007年 | 77篇 |
2006年 | 80篇 |
2005年 | 75篇 |
2004年 | 55篇 |
2003年 | 39篇 |
2002年 | 38篇 |
2001年 | 18篇 |
2000年 | 17篇 |
1999年 | 11篇 |
1998年 | 15篇 |
1997年 | 13篇 |
1996年 | 15篇 |
1995年 | 7篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 10篇 |
1991年 | 10篇 |
1990年 | 11篇 |
1989年 | 3篇 |
1988年 | 6篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有1537条查询结果,搜索用时 15 毫秒
81.
Mariana Pazos Estefania Dibello Juan Manuel Mesa Dalibor Sames Marcelo Alberto Comini Gustavo Seoane Ignacio Carrera 《Molecules (Basel, Switzerland)》2022,27(3)
The first stage of the drug discovery process involves the identification of small compounds with biological activity. Iboga alkaloids are monoterpene indole alkaloids (MIAs) containing a fused isoquinuclidine-tetrahydroazepine ring. Both the natural products and the iboga-inspired synthetic analogs have shown a wide variety of biological activities. Herein, we describe the chemoenzymatic preparation of a small library of novel N-indolylethyl-substituted isoquinuclidines as iboga-inspired compounds, using toluene as a starting material and an imine Diels–Alder reaction as the key step in the synthesis. The new iboga series was investigated for its potential to promote the release of glial cell line-derived neurotrophic factor (GDNF) by C6 glioma cells, and to inhibit the growth of infective trypanosomes. GDNF is a neurotrophic factor widely recognized by its crucial role in development, survival, maintenance, and protection of dopaminergic neuronal circuitries affected in several neurological and psychiatric pathologies. Four compounds of the series showed promising activity as GDNF releasers, and a leading structure (compound 11) was identified for further studies. The same four compounds impaired the growth of bloodstream Trypanosoma brucei brucei (EC50 1–8 μM) and two of them (compounds 6 and 14) showed a good selectivity index. 相似文献
82.
Pedro L. R. Guedes Carolina P. F. Carvalho Adriana A. F. Carbonel Manuel J. Simes Marcelo Y. Icimoto Jair A. K. Aguiar Maria Kouyoumdjian Marcos L. Gazarini Marcia R. Nagaoka 《Molecules (Basel, Switzerland)》2022,27(3)
During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL. 相似文献
83.
Junia O. Alves Bruno G. Botelho Marcelo M. Sena Rodinei Augusti 《Journal of mass spectrometry : JMS》2013,48(10):1109-1115
Direct infusion electrospray ionization mass spectrometry in the positive ion mode [ESI(+)‐MS] is used to obtain fingerprints of aqueous–methanolic extracts of two types of olive oils, extra virgin (EV) and ordinary (OR), as well as of samples of EV olive oil adulterated by the addition of OR olive oil and other edible oils: corn (CO), sunflower (SF), soybean (SO) and canola (CA). The MS data is treated by the partial least squares discriminant analysis (PLS‐DA) protocol aiming at discriminating the above‐mentioned classes formed by the genuine olive oils, EV (1) and OR (2), as well as the EV adulterated samples, i.e. EV/SO (3), EV/CO (4), EV/SF (5), EV/CA (6) and EV/OR (7). The PLS‐DA model employed is built with 190 and 70 samples for the training and test sets, respectively. For all classes (1–7), EV and OR olive oils as well as the adulterated samples (in a proportion varying from 0.5 to 20.0% w/w) are properly classified. The developed methodology required no ions identification and demonstrated to be fast, as each measurement lasted about 3 min including the extraction step and MS analysis, and reliable, because high sensitivities (rate of true positives) and specificities (rate of true negatives) were achieved. Finally, it can be envisaged that this approach has potential to be applied in quality control of EV olive oils. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
84.
Pereira CF Pimentel MF Galvão RK Honorato FA Stragevitch L Martins MN 《Analytica chimica acta》2008,611(1):41-47
This work presents a comparative study of calibration transfer among three near infrared spectrometers for determination of naphthenes and RON (Research Octane Number) in gasoline. Seven transfer methods are compared: direct standardization (DS), piecewise direct standardization (PDS), orthogonal signal correction (OSC), reverse standardization (RS), piecewise reverse standardization (PRS), slope and bias correction (SBC) and model updating (MU). Two pre-treatment procedures, namely standard normal variate (SNV) and multiplicative scatter correction (MSC), are also investigated. The choice of an appropriate number of transfer samples for each technique, as well as the effect of window size in PDS/PRS and OSC components, are discussed. A broad set of gasoline samples representative of the Northeastern states of Brazil is employed in the investigation. The results show that the use of calibration transfer yields prediction errors comparable to those obtained with complete recalibration of the secondary instrument. Overall, the results point to RS as the best method for the analytical problem under consideration. When storage and/or physical transportation of transfer samples are impractical, MU is more appropriate. The comprehensive investigation carried out in the present work will be of value for practitioners involved in networks of fuel monitoring. 相似文献
85.
An approach to control the spurious currents in a multiphase lattice Boltzmann method and to improve the implementation of initial condition
下载免费PDF全文
![点击此处可从《国际流体数值方法杂志》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Sébastien Leclaire Nicolas Pellerin Marcelo Reggio Jean‐Yves Trépanier 《国际流体数值方法杂志》2015,77(12):732-746
Multiphase lattice Boltzmann methods are known to generate spurious or parasitic currents at the fluid–fluid interfaces. This nonphysical phenomenon has to be avoided, or at least controlled, in order to achieve reliable solutions. In this article, a method to control these fictitious velocities via lattice refinement is proposed, which is based on interface thickness control for which both the spurious currents and the physical fluid–fluid interface thickness vanishes as the spatial resolution increases. It has been found that a proper interface thickness adjustment is required as the lattice refinement is applied, or an increase in spurious currents, instead of a reduction, can occur. By combining the new method with an appropriate multiphase flow initialization, the overall stability for high density O(1000) and viscosity O(100) ratios is greatly improved. Although this research has been conducted with a Rothman and Keller type lattice Boltzmann model, it is believed that other types of multiphase lattice Boltzmann models could benefit from the basic ideas underlying this research. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
86.
87.
Marcelo T. Oliveira Ana Flávia L. Specian Célia G.T.J. Andrade Emanuele J.G. Fran?a Luciana Furlaneto-Maia Marcia C. Furlaneto 《Micron (Oxford, England : 1993)》2010,41(6):604-608
Candida parapsilosis is found frequently as commensal organism on epithelial tissues, and is also an increasing cause of nosocomial infection. Scanning electron microscope (SEM) observations were used to analyse the capability of C. parapsilosis cells to adhere and grow as biofilm on human natural substrates and to compare the adherence pattern of isolates exhibiting distinct phenotypes. Cells from the crepe phenotype are predominantly elongated and form pseudohyphae whereas cells from the smooth phenotype are yeast-shaped, either in liquid cultures or on human nail and hair surfaces. The electron micrographs revealed that C. parapsilosis cells from the smooth phenotype adhered in higher number to both surfaces compared to the observed for the crepe phenotype. SEM analysis of human hair surface revealed that cells from the smooth phenotype appear as clumped blastoconidia of uniform morphology embedded in a flocculent extracellular material forming biofilm. The extracellular material and biofilm were seeing in a less extension in the crepe phenotype. A distinct adherence pattern was observed when human nail was used as substrate. Here C. parapsilosis cells seem to be linked to surface structures of human nail plate. Fibrillar extracellular material was observed connecting neighbouring cells as well as nail surface. 相似文献
88.
89.
CaII Binding Regulates and Dominates the Reactivity of a Transition‐Metal‐Ion‐Dependent Diesterase from Mycobacterium tuberculosis
下载免费PDF全文
![点击此处可从《Chemistry (Weinheim an der Bergstrasse, Germany)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dr. Marcelo M. Pedroso Prof. James A. Larrabee Dr. Fernanda Ely Shuhui E. Gwee Dr. Nataša Mitić Prof. David L. Ollis Prof. Lawrence R. Gahan Prof. Gerhard Schenk 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(3):999-1009
The diesterase Rv0805 from Mycobacterium tuberculosis is a dinuclear metallohydrolase that plays an important role in signal transduction by controlling the intracellular levels of cyclic nucleotides. As Rv0805 is essential for mycobacterial growth it is a promising new target for the development of chemotherapeutics to treat tuberculosis. The in vivo metal‐ion composition of Rv0805 is subject to debate. Here, we demonstrate that the active site accommodates two divalent transition metal ions with binding affinities ranging from approximately 50 nm for MnII to about 600 nm for ZnII. In contrast, the enzyme GpdQ from Enterobacter aerogenes, despite having a coordination sphere identical to that of Rv0805, binds only one metal ion in the absence of substrate, thus demonstrating the significance of the outer sphere to modulate metal‐ion binding and enzymatic reactivity. CaII also binds tightly to Rv0805 (Kd≈40 nm ), but kinetic, calorimetric, and spectroscopic data indicate that two CaII ions bind at a site different from the dinuclear transition‐metal‐ion binding site. CaII acts as an activator of the enzymatic activity but is able to promote the hydrolysis of substrates even in the absence of transition‐metal ions, thus providing an effective strategy for the regulation of the enzymatic activity. 相似文献
90.
Liu X McLaughlin AC de Miranda MP McInnes EJ Kilner CA Halcrow MA 《Chemical communications (Cambridge, England)》2002,(24):2978-2979
The complex [[Cu3(HpztBu)4(mu-pztBu)2(mu-F)2(mu 3-F)]2]F2 (HpztBu = 3[5]-tert-butylpyrazole) has a cyclic, C2v-symmetric hexacopper core. The two non-coordinated F- anions are encapsulated within cavities formed by three HpztBu ligands. 相似文献