首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   5733篇
  免费   152篇
  国内免费   42篇
化学   4272篇
晶体学   34篇
力学   158篇
数学   636篇
物理学   827篇
  2022年   37篇
  2021年   72篇
  2020年   85篇
  2019年   75篇
  2018年   55篇
  2017年   54篇
  2016年   106篇
  2015年   96篇
  2014年   99篇
  2013年   230篇
  2012年   358篇
  2011年   436篇
  2010年   205篇
  2009年   166篇
  2008年   364篇
  2007年   351篇
  2006年   384篇
  2005年   401篇
  2004年   301篇
  2003年   248篇
  2002年   263篇
  2001年   87篇
  2000年   97篇
  1999年   64篇
  1998年   63篇
  1997年   53篇
  1996年   94篇
  1995年   70篇
  1994年   55篇
  1993年   43篇
  1992年   43篇
  1991年   46篇
  1990年   29篇
  1989年   29篇
  1988年   28篇
  1987年   29篇
  1986年   23篇
  1985年   42篇
  1984年   46篇
  1983年   39篇
  1982年   36篇
  1981年   48篇
  1980年   43篇
  1979年   24篇
  1978年   47篇
  1977年   30篇
  1976年   34篇
  1975年   43篇
  1974年   31篇
  1973年   31篇
排序方式: 共有5927条查询结果,搜索用时 812 毫秒
971.
Excessive glucose production by the liver coupled with decreased glucose uptake and metabolism by muscle, fat, and liver results in chronically elevated blood glucose levels in patients with type 2 diabetes. Efforts to treat diabetes by reducing glucose production have largely focused on the gluconeogenesis pathway and rate-limiting enzymes within this pathway such as fructose-1,6-bisphosphatase (FBPase). The first potent FBPase inhibitors were identified using a structure-guided drug design strategy (Erion, M. D.; et al. J. Am. Chem. Soc. 2007, 129, 15480-15490) but proved difficult to deliver orally. Herein, we report the synthesis and characterization of a series of orally bioavailable FBPase inhibitors identified following the combined discoveries of a low molecular weight inhibitor series with increased potency and a phosphonate prodrug class suitable for their oral delivery. The lead inhibitor, 10A, was designed with the aid of X-ray crystallography and molecular modeling to bind to the allosteric AMP binding site of FBPase. High potency (IC50 = 16 nM) and FBPase specificity were achieved by linking a 2-aminothiazole with a phosphonic acid. Free-energy perturbation calculations provided insight into the factors that contributed to the high binding affinity. 10A and standard phosphonate prodrugs of 10A exhibited poor oral bioavailability (0.2-11%). Improved oral bioavailability (22-47%) was achieved using phosphonate diamides that convert to the corresponding phosphonic acid by sequential action of an esterase and a phosphoramidase. Oral administration of the lead prodrug, MB06322 (30, CS-917), to Zucker Diabetic Fatty rats led to dose-dependent inhibition of gluconeogenesis and endogenous glucose production and consequently to significant blood glucose reduction.  相似文献   
972.
A wide variety of highly substituted lactam containing peptidomimetic scaffolds are prepared by solid-phase synthesis from a single, versatile class of resin-bound aldehyde intermediates (1). These include monocyclics 3, bicyclics 4, tricyclics 5, and tetracyclics 6. The key intermediate 1 is readily synthesized from resin-bound natural or unnatural alpha-amino acids. The synthetic procedures permit the construction of a large diversity of substitution patterns for ready use in combinatorial chemistry. In every case, the release of final products from resin is by a cyclitive cleavage process. Since this depends on successful completion of multiple intermediate synthetic steps, the products are often quite pure, even though previous steps involve only a filtration workup. The mild conditions for many of these synthetic procedures offer the promise of using this chemistry in peptide fragment condensations to produce modified peptides, at either the N-terminus or C-terminus, or as individually assembled peptide segments with a wide variety of conformationally restricted peptidomimetic linkers at the point of juncture.  相似文献   
973.
Polyfluorenes without monoalkylfluorene defects   总被引:4,自引:0,他引:4  
  相似文献   
974.
Kulikov has given an étale morphism of degree d > 1 which is surjective modulo codimension two with X simply connected, settling his generalized jacobian problem. His method reduces the problem to finding a hypersurface and a subgroup of index d generated by geometric generators. By contrast we show that if D has simple normal crossings away from a set of codimension three and meets the hyperplane at infinity transversely, then necessarily d = 1. Received: 21 November 2006  相似文献   
975.
In this paper, we establish bounds on the degree of a symmetric polynomial p = p(x) = p(x 1,..., x g ) (with real coefficients) in g noncommuting (nc) variables x 1,..., x g in terms of the “signature” of its Hessian
which is a polynomial in x and h = (h 1,..., h g ) homogeneous of degree 2 in h. The bounds are obtained by exploiting the interplay between assorted representations for p(x) and p″(x)[h] that are developed in the paper. In particular, p″(x)[h] admits a representation of the form where f j + , f j are nc polynomials. Such representations are highly non-unique. However, there is a unique smallest number of positive (resp., negative) squares σ ± min required in an SDS decomposition of p″(x)[h]. Our main results yield the following corollary and a number of refinements. Supported by a Jay and Renee Weiss Chair. Partly supported by the NSF and the Ford Motor Co. Partly supported by the NSF grants DMS-0140112 and DMS-0457504.  相似文献   
976.
Abstract  Let p be a prime integer and M a Krull monoid with divisor class group . We represent by S the set of nontrivial divisor classes of which contain prime divisors. We present a new inequality for the elasticity of M (denoted ρ (M)) which is dependent on the cardinality of S and argue that this inequality is the best possible. If M as above has | S| = 3, then it is known that , but for large p, not all the values in this containment set can be realized. For each | S| = 3, we produce a submonoid of such that
Keywords: Krull monoid, Block monoid, Elasticity of factorization Mathematics Subject Classification (2000): 20M14, 20D60, 13F05  相似文献   
977.
This paper continues the study begun in [GEROLDINGER, A.: On non-unique factorizations into irreducible elements II, Colloq. Math. Soc. János Bolyai 51 (1987), 723–757] concerning factorization properties of block monoids of the form ℬ(ℤ n , S) where S = (hereafter denoted ℬ a (n)). We introduce in Section 2 the notion of a Euclidean table and show in Theorem 2.8 how it can be used to identify the irreducible elements of ℬ a (n). In Section 3 we use the Euclidean table to compute the elasticity of ℬ a (n) (Theorem 3.4). Section 4 considers the problem, for a fixed value of n, of computing the complete set of elasticities of the ℬ a (n) monoids. When n = p is a prime integer, Proposition 4.12 computes the three smallest possible elasticities of the ℬ a (p). Part of this work was completed while the second author was on an Academic Leave granted by the Trinity University Faculty Development Committee.  相似文献   
978.
Transmission mode ion/ion proton transfer reactions in a linear ion trap   总被引:1,自引:1,他引:0  
A new method is described for effecting ion/ion proton transfer reactions that involves storage of analyte ions while oppositely charged ions are transmitted through the stored ion population. In this approach, the products are captured and stored in the linear ion trap for subsequent mass analysis. Charge reduction of multiply charged protein ions is used as an example to illustrate the analytical usefulness of this method. In another variation of the transmission mode ion/ion reaction approach, two charge inversion experiments, implemented by passing analyte ions through a population of multiply charged reagent ions in a LIT, are also demonstrated. A pulsed dual ion source approach coupled with a hybrid triple quadrupole/linear ion trap instrument was used to demonstrate these two methods. The results for ion/ion reactions implemented using these so-called "transmission mode" experiments were comparable to those acquired using the more conventional mutual storage mode, both in terms of efficiency and information content of the spectra. An advantage of transmission mode experiments compared with mutual storage mode experiments is that they do not require any specialized measures to be taken to enable the simultaneous storage of oppositely charged ions.  相似文献   
979.
The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl/OCl(-)) is implicated in the pathogenesis of atherosclerosis and other inflammatory states. We have synthesized an imaging probe, sulfonaphthoaminophenyl fluorescein (SNAPF), that selectively reacts with HOCl. SNAPF detects HOCl produced by stimulated MPO-expressing cells cultured from human whole blood, as well as HOCl from bone marrow (BM)-derived macrophages isolated from transgenic mice that express human MPO. Two lines of evidence indicate that SNAPF permits the in vivo imaging of HOCl production. First, we used this approach to demonstrate HOCl production by neutrophils in experimental murine peritonitis. Second, we detected HOCl production by MPO expressing cells in human atherosclerotic arteries. Thus, fluorescence reflectance imaging by SNAPF may provide a valuable noninvasive molecular imaging tool for implicating HOCl and MPO in the damage of inflamed tissues.  相似文献   
980.
13C chemical shift tensor data from 2D FIREMAT spectra are reported for 4,7-di-t-butylacenaphthene and 4,7-di-t-butylacenaphthylene. In addition, calculations of the chemical shielding tensors were completed at the B3LYP/6-311G** level of theory. While the experimental tensor data on 4,7-di-t-butylacenaphthylene are in agreement with theory and with previous data on polycyclic aromatic hydrocarbons, the experimental and theoretical data on 4,7-di-t-butylacenaphthene lack agreement. Instead, larger than usual differences are observed between the experimental chemical shift components and the chemical shielding tensor components calculated on a single molecule of 4,7-di-t-butylacenaphthene, with a root mean square (rms) error of +/-7.0 ppm. The greatest deviation is concentrated in the component perpendicular to the aromatic plane, with the largest value being a 23 ppm difference between experiment and theory for the 13CH2 carbon delta11 component. These differences are attributed to an intermolecular chemical shift that arises from the graphitelike, stacked arrangement of molecules found in the crystal structure of 4,7-di-t-butylacenaphthene. This conclusion is supported by a calculation on a trimer of molecules, which improves the agreement between experiment and theory for this component by 14 ppm and reduces the overall rms error between experiment and theory to 4.0 ppm. This intermolecular effect may be modeled with the use of nuclei independent chemical shieldings (NICS) calculations and is also observed in the isotropic 1H chemical shift of the CH2 protons as a 4.2 ppm difference between the solution value and the solid-state chemical shift measured via a 13C-1H heteronuclear correlation experiment.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号