全文获取类型
收费全文 | 23522篇 |
免费 | 834篇 |
国内免费 | 125篇 |
专业分类
化学 | 15607篇 |
晶体学 | 243篇 |
力学 | 695篇 |
数学 | 2180篇 |
物理学 | 5756篇 |
出版年
2023年 | 149篇 |
2022年 | 416篇 |
2021年 | 571篇 |
2020年 | 428篇 |
2019年 | 433篇 |
2018年 | 382篇 |
2017年 | 360篇 |
2016年 | 675篇 |
2015年 | 578篇 |
2014年 | 815篇 |
2013年 | 1393篇 |
2012年 | 1699篇 |
2011年 | 1905篇 |
2010年 | 1206篇 |
2009年 | 1047篇 |
2008年 | 1605篇 |
2007年 | 1387篇 |
2006年 | 1431篇 |
2005年 | 1207篇 |
2004年 | 1071篇 |
2003年 | 898篇 |
2002年 | 848篇 |
2001年 | 527篇 |
2000年 | 473篇 |
1999年 | 329篇 |
1998年 | 210篇 |
1997年 | 205篇 |
1996年 | 270篇 |
1995年 | 184篇 |
1994年 | 197篇 |
1993年 | 202篇 |
1992年 | 151篇 |
1991年 | 123篇 |
1990年 | 125篇 |
1989年 | 97篇 |
1988年 | 68篇 |
1987年 | 72篇 |
1986年 | 50篇 |
1985年 | 74篇 |
1984年 | 50篇 |
1983年 | 42篇 |
1982年 | 63篇 |
1981年 | 62篇 |
1979年 | 46篇 |
1978年 | 45篇 |
1977年 | 34篇 |
1976年 | 41篇 |
1975年 | 37篇 |
1974年 | 36篇 |
1973年 | 34篇 |
排序方式: 共有10000条查询结果,搜索用时 9 毫秒
191.
Regueiro-Ren A Borzilleri RM Zheng X Kim SH Johnson JA Fairchild CR Lee FY Long BH Vite GD 《Organic letters》2001,3(17):2693-2696
[reaction: see text]. A series of 12alpha,13alpha-aziridinyl epothilone derivatives were synthesized in an efficient manner from epothilone A. The final semisynthetic route involves a formal double-inversion of stereochemistry at both the C12 and C13 positions. All aziridine analogues were tested for effects on tubulin binding polymerization and cytotoxicity. The results indicate that the aziridine moiety is a viable isosteric replacement for the epoxide in the case of epothilones. 相似文献
192.
Homologous recombination (HR) repair deficiency impairs the proper maintenance of genomic stability, thus rendering cancer cells vulnerable to loss or inhibition of DNA repair proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1). Inhibitors of nuclear PARPs are effective therapeutics for a number of different types of cancers. Here we review key concepts and current progress on the therapeutic use of PARP inhibitors (PARPi). PARPi selectively induce synthetic lethality in cancer cells with homologous recombination deficiencies (HRDs), the most notable being cancer cells harboring mutations in the BRCA1 and BRCA2 genes. Recent clinical evidence, however, shows that PARPi can be effective as cancer therapeutics regardless of BRCA1/2 or HRD status, suggesting that a broader population of patients might benefit from PARPi therapy. Currently, four PARPi have been approved by the Food and Drug Administration (FDA) for the treatment of advanced ovarian and breast cancer with deleterious BRCA mutations. Although PARPi have been shown to improve progression-free survival, cancer cells inevitably develop resistance, which poses a significant obstacle to the prolonged use of PARP inhibitors. For example, somatic BRCA1/2 reversion mutations are often identified in patients with BRCA1/2-mutated cancers after treatment with platinum-based therapy, causing restoration of HR capacity and thus conferring PARPi resistance. Accordingly, PARPi have been studied in combination with other targeted therapies to overcome PARPi resistance, enhance PARPi efficacy, and sensitize tumors to PARP inhibition. Moreover, multiple clinical trials are now actively underway to evaluate novel combinations of PARPi with other anticancer therapies for the treatment of PARPi-resistant cancer. In this review, we highlight the mechanisms of action of PARP inhibitors with or without BRCA1/2 defects and provide an overview of the ongoing clinical trials of PARPi. We also review the current progress on PARPi-based combination strategies and PARP inhibitor resistance.Subject terms: Cancer therapy, Mechanisms of disease, PolyADP-ribosylation 相似文献
193.
The metabolites of trimeprazine were identified in urine of rats by gas chromatography-mass spectrometry. After the oral administration of trimeprazine, the urinary metabolites were extracted with diethyl ether before or after hydrolysis with beta-glucuronidase. The identified metabolites were N-demethyltrimeprazine,3-hydroxytrimeprazine,N-demethyl-3-++ +hydroxytrimeprazine and trimeprazine sulphoxide. 相似文献
194.
Nanometer-sized metallic palladium particles can be synthesized by hydrogen reduction of Pd2+ ions dissolved in the water core of a water-in-CO2 microemulsion. The Pd nanoparticles, stabilized by the micromeulsion and uniformly dispersed in the supercritical fluid phase, are effective catalysts for hydrogenation of olefins. Examples of rapid and efficient hydrogenation of water-soluble and CO2-soluble olefins catalyzed by the Pd nanoparticles in supercritical CO2 are given. 相似文献
195.
Hyoung Sik Kim Min Kang Min Woo Song Jin Won Park Byoung Ryul Min 《Reaction Kinetics and Catalysis Letters》2004,81(2):251-257
Pt-Pd bimetallic catalysts were prepared in order to develop and investigate catalysts having excellent activity and stability
for benzene destruction. The effect of Pt addition to Pd catalysts is studied by XPS analysis.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
196.
The rate constant hydrolysis of α-(p-nitrophenyl)cinnamonitrile(NCPN) and its derivatives have been determined at various pH, and the rate equation which can
be applied over a wide pH range is obtained. On the basis of the rate equation, hydrolysis product, general base, and substituent
effects, a plausible mechanism of hydrolysis has been proposed: At pH < 4.0, the hydrolysis was initiated by the addition
of water to β-carbon of the carbon-carbon double bond. At pH > 8.5, the addition of hydroxide ion to the double bond was rate
controlling. In the range of pH 4.0–8.5, these two reactions occurred competitively.
Published in Russian in Kinetika i Kataliz, 2007, Vol. 48, No. 5, pp. 670–676.
This article was submitted by the authors in English. 相似文献
197.
Reaction of 1,6-enynes with a hydrosilane in the presence of immobilized cobalt/rhodium bimetallic nanoparticles gives 2-methyl-1-silylmethylidene-2-cyclopentanes in the absence of carbon monoxide and 2-formylmethyl-1-silylmethylidene-2-cyclopentanes under 1 atm of carbon monoxide, respectively. [reaction: see text] 相似文献
198.
A new approach to indolizines has been developed using a 5-endo-trig iodocyclization of allylic esters followed by isomerization and dehydroiodination facilitated by triethylamine at rt. This mild procedure enabled us to synthesize a number of highly substituted indolizines in good yields. 相似文献
199.
Jin-Woong?Kim Jin-Gyu?Park Jee-Hyun?Ryu Ih-Seop?Chang Kyung-Do?SuhEmail author 《Colloid and polymer science》2005,283(11):1233-1240
This study presents a method to produce monodisperse chloromethyl-functionalized macroporous poly(styrene-co-divinylbenzene) polymer particles by seeded polymerization in aqueous media. We observed that the molecular structure of
polystyrene seed particles, the composition of the secondary monomer mixtures, and the type of solvents were very important
factors that determine the morphology and porosity of the final particles. This study proposes that the molecular chemistry
of polystyrene seed polymers, increasing molecular weight or crosslinking, is another factor that can control the porosity
of the final particles. Also, the selection of a poor solvent was effective in forming the larger surface area. In this study,
it was confirmed that the chloromethyl groups introduced on the surface of porous particles were quantified chemically and
their effective incorporation had a close relationship with the surface area. 相似文献
200.
Lee JS Zhang MH Yun EK Geum D Kim K Kim TH Lim YS Seo JS 《Experimental & molecular medicine》2005,37(5):427-435
Vimentin is an intermediate filament that regulates cell attachment and subcellular organization. In this study, vimentin filaments were morphologically altered, and its soluble subunits were rapidly reduced via cadmium chloride treatment. Cadmium chloride stimulated three major mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, and led apoptotic pathway via caspase-9 and caspase-3 activations. In order to determine whether MAPKs were involved in this cadmium-induced soluble vimentin disappearance, we applied MAPK-specific inhibitors (PD98059, SP600125, SB203580). These inhibitors did not abolish the cadmium-induced soluble vimentin disappearance. Caspase and proteosome degradation pathway were also not involved in soluble vimentin disappearance. When we observed vimentin levels in soluble and insoluble fractions, soluble vimentin subunits shifted to an insoluble fraction. As we discovered that heat-shock protein 27 (HSP27) was colocalized and physically associated with vimentin in unstressed cells, the roles of HSP27 with regard to vimentin were assessed. HSP27-overexpressing cells prevented morphological alterations of the vimentin filaments, as well as reductions of soluble vimentin, in the cadmium-treated cells. Moreover, HSP27 antisense oligonucleotide augmented these cadmium-induced changes in vimentin. These findings indicate that HSP27 prevents disruption of the vimentin intermediate filament networks and soluble vimentin disappearance, by virtue of its physical interaction with vimentin in cadmium-treated SK-N-SH cells. 相似文献