全文获取类型
收费全文 | 8830篇 |
免费 | 309篇 |
国内免费 | 75篇 |
专业分类
化学 | 6433篇 |
晶体学 | 41篇 |
力学 | 202篇 |
数学 | 1341篇 |
物理学 | 1197篇 |
出版年
2023年 | 33篇 |
2021年 | 100篇 |
2020年 | 145篇 |
2019年 | 141篇 |
2018年 | 101篇 |
2017年 | 73篇 |
2016年 | 220篇 |
2015年 | 189篇 |
2014年 | 222篇 |
2013年 | 515篇 |
2012年 | 540篇 |
2011年 | 681篇 |
2010年 | 307篇 |
2009年 | 237篇 |
2008年 | 518篇 |
2007年 | 598篇 |
2006年 | 626篇 |
2005年 | 502篇 |
2004年 | 458篇 |
2003年 | 387篇 |
2002年 | 310篇 |
2001年 | 108篇 |
2000年 | 66篇 |
1999年 | 66篇 |
1998年 | 60篇 |
1997年 | 89篇 |
1996年 | 103篇 |
1995年 | 79篇 |
1994年 | 75篇 |
1993年 | 88篇 |
1992年 | 70篇 |
1991年 | 56篇 |
1990年 | 82篇 |
1989年 | 44篇 |
1988年 | 59篇 |
1987年 | 59篇 |
1986年 | 70篇 |
1985年 | 107篇 |
1984年 | 104篇 |
1983年 | 68篇 |
1982年 | 95篇 |
1981年 | 93篇 |
1980年 | 94篇 |
1979年 | 68篇 |
1978年 | 84篇 |
1977年 | 63篇 |
1976年 | 58篇 |
1975年 | 52篇 |
1974年 | 32篇 |
1973年 | 59篇 |
排序方式: 共有9214条查询结果,搜索用时 15 毫秒
991.
992.
993.
Weak slice conditions are introduced and imbeddings of Sobolevspaces in various Lipschitz-type spaces are investigated. 相似文献
994.
Discovery of a potent,selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy 总被引:3,自引:0,他引:3
Szczepankiewicz BG Liu G Hajduk PJ Abad-Zapatero C Pei Z Xin Z Lubben TH Trevillyan JM Stashko MA Ballaron SJ Liang H Huang F Hutchins CW Fesik SW Jirousek MR 《Journal of the American Chemical Society》2003,125(14):4087-4096
Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that downregulates the insulin receptor. Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention. In this work, NMR-based screening identified a nonselective competitive inhibitor of PTP1B. A second site ligand was also identified by NMR-based screening and then linked to the catalytic site ligand by rational design. X-ray data confirmed that the inhibitor bound with the catalytic site in the native, "open" conformation. The final compound displayed excellent potency and good selectivity over many other phosphatases. The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases. 相似文献
995.
Plaut DJ Martin SM Kjaer K Weygand MJ Lahav M Leiserowitz L Weissbuch I Ward MD 《Journal of the American Chemical Society》2003,125(51):15922-15934
Crystalline ternary inclusion monolayers consisting of a two-dimensional hydrogen-bonded host network of guanidinium (G) ions and organosulfonate (S) amphiphiles, and biphenylalkane guests, can be generated at the air-water interface through synergistic structural enforcement by hydrogen bonding and host-guest packing. Surface pressure-area isotherms of the 4'-hexadecylbiphenyl-4-sulfonate (C16BPS) amphiphile in the presence of G, with or without guest, are characterized by lift-off molecular areas expected for the GS sheet based on single-crystal X-ray structures of homologous bulk crystals. Intercalation of biphenylalkane guests (4-C(n)()H(2)(n)()(+1)-C(6)H(4)-C(6)H(5), n = 1, 4, 6, 10, 16; denoted CnBP) between organosulfonate hydrophobes, which define pocketlike cavities in the GS monolayer host, afford ternary inclusion monolayers with a 1:1 host-guest stoichiometry. These inclusion monolayers are less compressible than the guest-free host, consistent with dense packing of the biphenylalkane moieties of the host and the biphenylalkane guests. The inclusion monolayers are distinguished from the amorphous guest-free host and from selected guanidinium-free mixed monolayers by structural characterization with grazing-angle incidence X-ray diffraction (GIXD). The GIXD data for the ternary (G)C16BPS:C16BP and (G)C16BPS:C6BP inclusion monolayers obtained upon compression are consistent with a rectangular unit cell. The dimensions of these unit cells and refinement of the GIXD data suggest a "rotated shifted ribbon" GS hydrogen-bonding motif similar to that observed in some bulk GS crystals, including (G)(ethylbiphenylsulfonate). GIXD reveals that (G)C16BPS:C16BP and (G)C16BPS:C6BP are more crystalline than the corresponding guanidinium-free mixed monolayers. The (G)C16BPS:C6BP inclusion monolayer is stable upon compression, even though the alkyl-alkyl host-guest interactions are reduced due to the shorter hexyl substituents of the guest, demonstrating an important reinforcing role for the hydrogen-bonded GS sheet. The structure of a C16BPS:tetracosane (C24) mixed monolayer is independent of G; the unit cell symmetry and dimensions suggest a structure governed by alkyl-alkane interactions that prohibit formation of a GS network. These results illustrate that the existence of ternary inclusion monolayers with an intact GS network requires guest molecules that are structurally homologous with the hydrophobes of the host, in this case biphenylalkanes. The observation of these inclusion compounds suggests an approach for introducing functional nonamphiphilic molecules to an air-water interface through inclusion in a well-defined host. 相似文献
996.
Starch and its analogue glycogen are biosynthesized by enzymes that have been classified by sequence similarities into two families that have no significant sequence overlap: the animal/fungal glycogen synthases and the plant/bacterial glycogen (starch) synthases. Recent gene sequence analysis of putative archaea enzymes implicates them as a third family that links the structural and functional features of the other two classes. Herein, we present the first rapid electrospray ionization mass spectrometry-based assay to quantify any carbohydrate-polymerizing activity, the first cloning and recombinant expression as well as verification of the putative function of a glycogen synthase from the hyperthermophilic archaea Pyrococcus furiosus, and the characterization of a variety of glycogen synthases with the new assay. The new assay allowed the determination of Km and Vmax values for the rabbit, yeast, and P. furiosus glycogen synthases. Most surprisingly, unlike the synthases from rabbit or yeast and in contradiction to what would be expected from structural studies of other nucleotide-sugar binding proteins, the synthase from the archaea source accepts both uridine- and adenine-diphosphate activated glucose competitively and with comparable affinities to form a glucose polymer. This loose substrate specificity implicates this protein as the chemical link between the two branches of glycogen synthases that have evolved to accept primarily one or the other nucleotide as well as a good source enzyme for polymer bioengineering efforts. 相似文献
997.
Yu L Oost TK Schkeryantz JM Yang J Janowick D Fesik SW 《Journal of the American Chemical Society》2003,125(15):4444-4450
A method is described for the NMR-based screening for the discovery of aminoglycoside mimetics that bind to Escherichia coli A-site RNA. Although aminoglycosides are clinically useful, they exhibit high nephrotoxicity and ototoxicity, and their overuse has led to the development of resistance to important microbial pathogens. To identify a new series of aminoglycoside mimetics that could potentially overcome the problems associated with toxicities and resistance development observed with the aminoglycosides, we have prepared large quantities of E. coli 16 S A-site RNA and conducted an NMR-based screening of our compound library in search for small-molecule RNA binders against this RNA target. From these studies, several classes of compounds were identified as initial hits with binding affinities in the range of 70 microM to 3 mM. Lead optimization through synthetic modifications of these initial hits led to the discovery of several small-molecule aminoglycoside mimetics that are structurally very different from the known aminoglycosides. Structural models of the A-site RNA/ligand complexes were prepared and compared to the three-dimensional structures of the RNA/aminoglycoside complexes. 相似文献
998.
7-Hydroxy-1-naphthalenesulfonate (2-naphthol-8-sulfonate) monoanion demonstrates proton transfer in the lowest excited singlet state in DMSO-water mixtures as well as in pure water. The dissociation reaction of the directly excited monoanion is strongly solvent-dependent, and independent of solution acidity. The reprotonation of the conjugate base, however, depends predominantly on the acidity of the solution and only on the continuum properties of the solvent. The separability of the dissociation and reprotonation reactions, using steady-state methodology, allows the reprotonation to be treated independent of the dissociation. The linear relationship between the ratio of the relative fluorescence efficiencies of acid and conjugate base, and the hydrogen ion concentration is obtained only if proper Br?nsted activity factors are included in the relationship. These factors can be calculated from classical electrostatics and are the fourth powers of the activity coefficients necessary to convert the formal hydrogen ion concentration to hydrogen ion activity. Using this approach, pH was calculated from hydrogen ion concentration in DMSO-water solutions, containing a mole fraction of DMSO up to about 0.4. 相似文献
999.
Mills SJ Riley AM Liu C Mahon MF Potter BV 《Chemistry (Weinheim an der Bergstrasse, Germany)》2003,9(24):6207-6214
New and rapid syntheses of the enantiomeric intracellular signalling molecules d-myo-inositol 1,4,5,6-tetrakisphosphate (1 a) and D-myo-inositol 3,4,5,6-tetrakisphosphate (1 b) are described. The synthetic strategy employs the novel butane-2,3-diacetal-protected (BDA-protected) myo-inositol (+/-)-3 ab, directly accessible from myo-inositol on a large scale, and an optical resolution with diastereoisomeric (R)-(-)-acetylmandelate esters. The X-ray crystal structure of (+/-)-4, an unusual side product of acid-catalysed reaction of myo-inositol with butanedione is also presented, and the absolute configurations of 1 a and 1 b are definitively assigned by conversion of key precursors into (+)-bornesitol and L-iditol hexaacetate, respectively. Biological activity of synthetic 1 b was confirmed in comparison with the natural polyphosphate. 相似文献
1000.
Reaction of the phosphavinyl Grignard reagent [Z-MesP=C(Bu(t))MgBr.OEt2]2 (Mes = 2,4,6-Me3C6H2) with MesPCl2 affords the corresponding 1,3-diphosphapropene compound [Z-MesP=C(Bu(t))P(X)Mes] (X = Cl, Br); subsequent reaction with two equivalents of elemental lithium in thf affords the title compound [[Bu(t)C(PMes)2]Li(thf)3], which contains an asymmetric eta1-1,3-diphosphaallyl ligand. 相似文献