全文获取类型
收费全文 | 1512篇 |
免费 | 116篇 |
国内免费 | 157篇 |
专业分类
化学 | 1637篇 |
晶体学 | 7篇 |
力学 | 2篇 |
综合类 | 22篇 |
数学 | 12篇 |
物理学 | 105篇 |
出版年
2024年 | 3篇 |
2023年 | 37篇 |
2022年 | 189篇 |
2021年 | 164篇 |
2020年 | 100篇 |
2019年 | 55篇 |
2018年 | 51篇 |
2017年 | 43篇 |
2016年 | 83篇 |
2015年 | 67篇 |
2014年 | 82篇 |
2013年 | 106篇 |
2012年 | 87篇 |
2011年 | 73篇 |
2010年 | 57篇 |
2009年 | 65篇 |
2008年 | 67篇 |
2007年 | 47篇 |
2006年 | 68篇 |
2005年 | 47篇 |
2004年 | 41篇 |
2003年 | 41篇 |
2002年 | 26篇 |
2001年 | 18篇 |
2000年 | 23篇 |
1999年 | 22篇 |
1998年 | 21篇 |
1997年 | 21篇 |
1996年 | 11篇 |
1995年 | 13篇 |
1994年 | 11篇 |
1993年 | 9篇 |
1992年 | 11篇 |
1991年 | 10篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1982年 | 1篇 |
排序方式: 共有1785条查询结果,搜索用时 15 毫秒
31.
Summary We have carried out up to 8.0 ns molecular dynamics simulation on the ATP-bound complexes of EGFR and HER-2 (homology model)
receptor kinase domains to explore the possible consequences of amino acid residue changes in or close to the ATP site that
might provide insights for selectivity of these kinases towards ATP site inhibitors. The simulation results show the formation
of a channel under Thr766 following the movement of the side chain of Gln767 away from the hinge in EGFR. In HER-2, a similar
movement of Gln799 occurs, but a simultaneous movement of Arg784 towards the hinge region occurs that tends to close the channel.
The movement of Arg784 in HER-2 appears to result from the absence of an anchoring residue like Asp746 in EGFR, which has
been changed to Gly778 in HER-2. In EGFR, this Arg784 is held away from the hinge region by interaction with Asp746, thereby
leaving the channel open. This might be an important contributory factor to differences in selectivity of the ligands between
the two kinases, probably more so than the conservative change of Cys751 of EGFR to serine in HER-2 at the ATP site. 相似文献
32.
Poly(acrylonitrile-methylmethacrylate-sodium vinylsulfonate) membranes were subjected to seven different chemical modifications and the amount of the newly formed groups was measured for each membrane. Urease was then covalently immobilized onto the modified membranes and the amount of bound protein was determined. The kinetic parameters V(max) and K(m) of the immobilized urease were studied under static and dynamic conditions. Results showed that the rate of the enzyme reaction was higher for the membranes modified with NH(2)OH . H(2)SO(4), NH(2)NH(2) . H(2)SO(4), NaOH + EDA and NaOH + GA + EDA. It was confirmed that the reaction rate, measured under dynamic conditions, was higher than that one determined under static conditions. The influence of Cu(II) ions, as inhibitors, on the enzyme reaction kinetics (V(i) and K(i)) was also investigated. It turned out that the most sensitive membranes towards Cu(II) were those modified with NH(2)NH(2) . H(2)SO(4), NaOH + EDA and H(2)O(2). The results initiated further investigations on the influence of other heavy metal ions (Cd(II), Zn(II), Ni(II) and Pb(II)) over urease bound to a NH(2)OH . H(2)SO(4)-modified membrane. It was found that the inhibition effect of the heavy metal ions over immobilized urease decreases in the order: Cu(II) > Cd(II) > Zn(II) > Ni(II) > Pb(II). [Diagram: see text] 相似文献
33.
C. S. Bentivoglio Ruiz L. D. B. Machado J. E. Volponi E. Segura Pino 《Journal of Thermal Analysis and Calorimetry》2004,75(2):507-512
Radiation curing is an environmentally-friendly technology. Furthermore, radiation curing is a faster, energy saving and more
efficient industrial process than the heat-curable process. One of the most important requirements for the widespread application
of UV curable coatings in the coating industry is that they are stable vs. atmospheric degradation. Today's state of the art
in oxidative drying and thermosetting coatings is the use of light stabilizers to protect polymers vs. the damage of outdoor
exposure. Oxygen has a detrimental effect on the cure response of free radical systems, especially in thin-film coatings.
Differential photocalorimetry (photo-DSC) was used to investigate the oxygen effect and the use of light stabilizers on UV
curing of photocurable formulations based on acrylate materials. Coating thickness influence was also considered.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
34.
Cellulose-based hydrogel materials were prepared and modified with tannic acid and l-methionine using ionic liquid as the solvent. The gels were prepared to develop a sustained release medium for selenourea (SeU). The drug delivery characteristics of selenourea-loaded cellulose (CSeU), selenourea-loaded tannic acid-modified cellulose (CTSeU), and selenourea-loaded L-methionine-modified cellulose (CMSeU) were investigated in aqueous media and simulated gastric fluid (SGF) media. This modified gel beads have been characterized using field emission scanning electron microscope, X-ray energy-dispersive spectroscopy, Fourier transform infrared spectroscopy, thermogravimetry–differential thermal analysis and swelling properties and compared with those of the unmodified ones. We also investigated the inhibitory effects of SeU released from these gels on the activity of mushroom tyrosinase. Out of all the gel materials, CTSeU showed maximum SeU release both in water and SGF media. However, tyrosinase inhibitory action in PBS medium was comparable for all the three gel materials. 相似文献
35.
New conformationally restricted analogues of tumor promoter (−)-indolactam-V (1), indolinelactam-Vs (8, 11) and their hexyl derivatives at position 1 or 7 (9, 10, 12, 13), were synthesized from 1. (3R)-Indolinelactam-V (8) adopted a conformation similar to the twist form of 1 with a cis amide, while the conformation of (3S)-indolinelactam-V (11) was close to that of the sofa form of 1 with a trans amide. 7-Hexyl derivatives of 8 and 11 (10, 13) showed binding affinities for C1 domains of protein kinase C (PKC) isozymes compared to 1, but exhibited little selectivity among these PKC isozymes. However, introduction of the hexyl group at position 1 of 8 and 11 significantly enhanced their binding selectivity for novel PKC isozymes. The best selectivity for novel PKC isozymes was observed in (3S)-1-hexylindolinelactam-V (12) with a sofa-like conformation. These results suggest that a sofa-restricted analogue of 1 with a hydrophobic chain at an appropriate position would be a promising lead for designing agents with a high selectivity for novel PKC isozymes. 相似文献
36.
The heterocyclic nucleus s-triazino[1,2-a]benzimidazole has been reported to exhibit antibacterial activity. In this study, seven new 3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazole derivatives were prepared via cyclocondensation between 2-guanidinobenzimidazole and fluorine substituted (including trifluoromethyl) benzaldehydes. The structures of all the compounds were confirmed by 1H, 13C NMR and IR spectral data. Spectral data also suggested the existence of various tautomeric forms of the fluorine-containing s-triazino[1,2-a]benzimidazole compounds. The synthesized compounds were also screened for antibacterial and bovine dihydrofolate reductase (DHFR) inhibitory activities. The compound 3g substituted with a 3′,5′-bis(trifluoromethyl)phenyl moiety demonstrated the best antibacterial activity in the series. None of the tested compounds significantly inhibited bovine DHFR. 相似文献
37.
Matioli Graciette Zanin Gisella M. De Moraes Flávio F. 《Applied biochemistry and biotechnology》2002,98(1-9):947-961
The influence of substrate or product level on the initial velocity of cyclodextrin (CD) production by cyclodextringlycosyltransferase
from a Brazilian isolate of Bacillus firmus was studied. Our results indicate that the product γ-CD is a stronger inhibitor to the reaction than β-CD. Small saccharides
could also inhibit CD production, although to a lesser extent than the products, and maltose was the strongest inhibitor among
small saccharides. Increasing substrate concentration resulted in greater reduction on enzyme activity for the formation of
β-CD than for γ-CD. We modeled the kinetics of CD production with a set of four reversible reactions including the cyclization/coupling
reaction that forms/opens CDs, and three disproportionation reactions. Our model on the initial velocity data explained well
the substrate inhibition phenomenon. Kinetic parameters were determined by fitting the initial velocity data into our model. 相似文献
38.
咪唑类化合物-CuCl络合催化剂在甲醇氧化羰基化反应中的催化性能 总被引:21,自引:0,他引:21
研究了咪唑及其衍生物配合CuCl对甲醇液相氧化羰化合成碳酸二甲酯的催化性能。筛选出溶解性好、腐蚀性小且催化活性高的多功能助催剂。实验结果表明,反应体系中加入N-甲基咪唑后,CuCl可以完全溶解。当催化剂的浓度为0.2 mol/L, N-甲基咪唑与CuCl的量为4∶1,反应温度为120 ℃,反应压力为2.40 MPa,CO与O2的进气比2∶1,反应3 h的条件下甲醇的摩尔转化率为15.4%,选择性为98%以上。从腐蚀性试验结果看,50 ℃时,加入N-甲基咪唑化合物后,Q235钢在CuCl/CH3OH/H2O/CO/O2体系中的腐蚀速率为0.22mm/a,缓蚀效率为94.5%。动力学研究表明,反应近似为一级,加入N-甲基咪唑后,反应速率常数为0.15 min-1。 相似文献
39.
Three-dimensional quantitative structure-activity relationships of steroid aromatase inhibitors 总被引:1,自引:0,他引:1
Summary Inhibition of aromatase, a cytochrome P450 that converts androgens to estrogens, is relevant in the therapeutic control of breast cancer. We investigate this inhibition using a three-dimensional quantitative structure-activity relationship (3D QSAR) method known as Comparative Molecular Field Analysis, CoMFA [Cramer III, R.D. et al., J. Am. Chem. Soc., 110 (1988) 5959]. We analyzed the data for 50 steroid inhibitors [Numazawa, M. et al., J. Med. Chem., 37 (1994) 2198, and references cited therein] assayed against androstenedione on human placental microsomes. An initial CoMFA resulted in a three-component model for log(1/Ki), with an explained variance r2 of 0.885, and a cross-validated q2 of 0.673. Chemometric studies were performed using GOLPE [Baroni, M. et al., Quant. Struct.-Act. Relatsh., 12 (1993) 9]. The CoMFA/GOLPE model is discussed in terms of robustness, predictivity, explanatory power and simplicity. After randomized exclusion of 25 or 10 compounds (repeated 25 times), the q2 for one component was 0.62 and 0.61, respectively, while r2 was 0.674. We demonstrate that the predictive r2 based on the mean activity (Ym) of the training set is misleading, while the test set Ym-based predictive r2 index gives a more accurate estimate of external predictivity. Using CoMFA, the observed differences in aromatase inhibition among C6-substituted steroids are rationalized at the atomic level. The CoMFA fields are consistent with known, potent inhibitors of aromatase, not included in the model. When positioned in the same alignment, these compounds have distinct features that overlap with the steric and electrostatic fields obtained in the CoMFA model. The presence of two hydrophobic binding pockets near the aromatase active site is discussed: a steric bulk tolerant one, common for C4, C6-alpha and C7-alpha substitutents, and a smaller one at the C6-beta region. 相似文献
40.
Oliveira SC Paiva TC Visconti AE Giudici R 《Applied biochemistry and biotechnology》1998,74(3):161-172
Discrimination between different rival models for describing the inhibitory effect of ethanol both on yeast growth and on
fermentation was studied for a continuous process of alcoholic fermentation in a tower reactor with recycling of flocculating
cells. Models tested include linear, parabolic, hyperbolic, exponential, and generalized nonlinear power-law types. The best
expressions were identified under the criteria that all the kinetic parameters should assume acceptable values in a feasible
range and should result in the best fit of the experimental data. The kinetic parameters were estimated from steady-state
data of several sugar concentrations in feeding stream (S0 = 160, 170, 180, 190, 200 g/L), constant dilution rate (D = 0.2 h-1), recycle ratio (α = 13.6), and temperature (T = 30°C). The best model for the yeast growth was of power-law type, whereas
for the product formation the best model was of linear type. These models were able to reproduce the trends of the process
variables satisfactorily. 相似文献