全文获取类型
收费全文 | 1471篇 |
免费 | 114篇 |
国内免费 | 3篇 |
出版年
2023年 | 16篇 |
2022年 | 10篇 |
2021年 | 18篇 |
2020年 | 10篇 |
2019年 | 18篇 |
2018年 | 47篇 |
2017年 | 23篇 |
2016年 | 43篇 |
2015年 | 91篇 |
2014年 | 92篇 |
2013年 | 99篇 |
2012年 | 102篇 |
2011年 | 116篇 |
2010年 | 69篇 |
2009年 | 59篇 |
2008年 | 91篇 |
2007年 | 83篇 |
2006年 | 65篇 |
2005年 | 65篇 |
2004年 | 60篇 |
2003年 | 58篇 |
2002年 | 38篇 |
2001年 | 14篇 |
2000年 | 16篇 |
1999年 | 19篇 |
1997年 | 6篇 |
1992年 | 16篇 |
1991年 | 21篇 |
1990年 | 12篇 |
1989年 | 14篇 |
1988年 | 23篇 |
1987年 | 15篇 |
1986年 | 15篇 |
1985年 | 23篇 |
1984年 | 13篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 13篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 8篇 |
1975年 | 3篇 |
1974年 | 7篇 |
1973年 | 11篇 |
1972年 | 8篇 |
1971年 | 6篇 |
1970年 | 7篇 |
1965年 | 3篇 |
排序方式: 共有1588条查询结果,搜索用时 15 毫秒
951.
Katherine Nott Gaëtan Richard Pascal Laurent Christine Jérôme Christophe Blecker Jean-Paul Wathelet Michel Paquot Magali Deleu 《Process Biochemistry》2013,48(1):133-143
New rhamnolipids were obtained via the development of a synthesis procedure consisting of two biocatalyzed steps. In the first step, naringinase was used to introduce a primary alcohol function onto rhamnose by glycosylation of 1,3-propanediol. In the second step, immobilized lipase B from Candida antarctica catalyzed the esterification of the primary hydroxyl group with mono- and di-carboxylic fatty acids of increasing chain length (from C8 to C14). For the monoic acids, the initial rate and 24 h yield decreased with increasing chain length. For the dioic acid, the number of carbon atoms of the acid did not influence these parameters. The new rhamnolipid obtained with tetradecanoic acid showed very good surface properties. At pH 5, it had a very low critical aggregation concentration of 1.70 μM and it diminished water's surface tension to 27.6 mN/m. It was also able to form stable insoluble monolayers. On the other hand, the rhamnolipid formed with tetradecanedioic acid showed far less interesting surface properties. 相似文献
952.
Radek Gažák Kateřina Fuksová Petr Marhol Marek Kuzma Rajesh Agarwal Vladimír Křen 《Process Biochemistry》2013,48(1):184-189
The flavonolignan isosilybin (1) is one of the silybin congeners contained in the silymarin complex, which is isolated from the seeds of the milk thistle (Silybum marianum). A number of recent studies have demonstrated that isosilybin is probably the most potent anticancer agent found in silymarin. It occurs as a mixture of two diastereoisomers, A and B. Lipase Novozym 435 was found to allow the preparative production of both optically pure isosilybin A and B in a diastereoisomeric purity of over 95%. A preparatory method based on the enzymatic resolution and other purification methods has been developed, enabling multigram amounts of both optically pure isosilybins A (1a) and B (1b) to be obtained. 相似文献
953.
Nadine Galonde Yves Brostaux Gaëtan Richard Katherine Nott Christine Jerôme Marie-Laure Fauconnier 《Process Biochemistry》2013,48(12):1914-1920
The purpose of the present study is to find the conditions allowing to reach the highest 24 h-yield (24 h-η) for the synthesis of mannosyl myristate catalyzed by the immobilized lipase B from Candida antarctica (Novozym® 435) in the ionic liquid (IL) [Bmpyrr][TFO] (1-butyl-1-methylpyrrolidinium trifluoromethanesulfonate). A full factorial design (FFD) was used in order to study the influence of three variables (temperature, mannose/vinyl myristate ratio and total substrate quantity) on the 24 h-η. This design led to a model based on a second order polynomial response function. The resulting predicted contour plots have shown that the highest 24 h-η should be obtained with high temperatures, low sugar/vinyl ester molar ratio and intermediate total substrate quantities (mmol). The model has been successfully verified and experimentally confirmed at the optimal conditions of 80 °C, substrate molar ratio of 1/10 and total substrate quantity of 0.26 mmol leading to the highest predicted 24 h-η of 72.2%. 相似文献
954.
955.
Ophélie Saison-Francioso Gaëtan Lévêque Abdellatif Akjouj Yan Pennec Bahram Djafari-Rouhani Rabah Boukherroub Sabine Szunerits 《Plasmonics (Norwell, Mass.)》2013,8(4):1691-1698
The sensitivity of the wavelength position of localized surface plasmon resonance (LSPR) in metal nanostructures to local changes in the refractive index has been widely used for label-free detection strategies. Tuning the optical properties of the nanostructures from the visible to the infrared region is expected to have a drastic effect on the refractive index sensitivity. Here, we theoretically investigate the optical response of a newly designed plasmonic interface to changes in the bulk refractive index by the finite difference time domain method. It consists of a structured interface, where the planar interface is superposed with dielectric pillars 30 nm in height and 125 nm in length with a separation distance of 15 nm. The pillars are covered with U-shaped gold nanostructures of 50 nm in height, 125 nm in length, and 5 nm of gold base thickness. The whole structure is finally covered with a 5-nm thick dielectric layer of n 2?=?2.63. This plasmonic structure shows bulk refractive index sensitivities up to 1750 nm/RIU (RIU : refractive index unit) in the near infrared (λ?=?2621 nm). The enhanced sensitivity is a consequence of the extremely enhanced electrical field between the gold nanopillars of the plasmonic interface. 相似文献
956.
Erfan Aref-Eshghi Jennifer Kerkhof Victor P. Pedro Groupe DI France Mouna Barat-Houari Nathalie Ruiz-Pallares Jean-Christophe Andrau Didier Lacombe Julien Van-Gils Patricia Fergelot Christéle Dubourg Valerie Cormier-Daire Sophie Rondeau François Lecoquierre Pascale Saugier-Veber Gaël Nicolas Gaetan Lesca Nicolas Chatron Bekim Sadikovic 《American journal of human genetics》2021,108(6):1161-1163
957.
Pellissier LP Barthet G Gaven F Cassier E Trinquet E Pin JP Marin P Dumuis A Bockaert J Banères JL Claeysen S 《The Journal of biological chemistry》2011,286(12):9985-9997
The discovery that class C G protein-coupled receptors (GPCRs) function as obligatory dimeric entities has generated major interest in GPCR oligomerization. Oligomerization now appears to be a common feature among all GPCR classes. However, the functional significance of this process remains unclear because, in vitro, some monomeric GPCRs, such as rhodopsin and β(2)-adrenergic receptors, activate G proteins. By using wild type and mutant serotonin type 4 receptors (5-HT(4)Rs) (including a 5-HT(4)-RASSL) expressed in COS-7 cells as models of class A GPCRs, we show that activation of one protomer in a dimer was sufficient to stimulate G proteins. However, coupling efficiency was 2 times higher when both protomers were activated. Expression of combinations of 5-HT(4), in which both protomers were able to bind to agonists but only one could couple to G proteins, suggested that upon agonist occupancy, protomers did not independently couple to G proteins but rather that only one G protein was activated. Coupling of a single heterotrimeric G(s) protein to a receptor dimer was further confirmed in vitro, using the purified recombinant WT RASSL 5-HT(4)R obligatory heterodimer. These results, together with previous findings, demonstrate that, differently from class C GPCR dimers, class A GPCR dimers have pleiotropic activation mechanisms. 相似文献
958.
Jung Ok Lee Soo Kyung Lee Jin Hee Jung Ji Hae Kim Ga Young You Su Jin Kim Sun Hwa Park Kyung‐Ok Uhm Hyeon Soo Kim 《Journal of cellular physiology》2011,226(4):974-981
Metformin is a major oral anti‐diabetic drug and is known as an insulin sensitizer. However, the mechanism by which metformin acts is unclear. In this study, we found that AICAR, an AMPK activator, and metformin increased the expression of Rab4 mRNA and protein levels in skeletal muscle C2C12 cells. The promoter activity of Rab4 was increased by metformin in an AMPK‐dependent manner. Metformin stimulated the phosphorylation of AS160, Akt substrate, and Rab GTPase activating protein (GAP), and also increased the phosphorylation of PKC‐zeta, which is a critical molecule for glucose uptake. Knockdown of AMPK blocked the metformin‐induced phosphorylation of AS160/PKC‐zeta. In addition, a colorimetric absorbance assay showed that insulin‐induced translocation of GLUT4 was suppressed in Rab4 knockdown cells. Moreover, Rab4 interacted with PKC‐zeta but not with GLUT4. The C‐terminal‐deleted Rab4 mutant, Rab4ΔCT, showed diffuse sub‐cellular localization, while wild‐type Rab4 localized exclusively to the perinuclear membrane. Unlike Rab4ΔCT, wild‐type Rab4 co‐localized with PKC‐zeta. Together, these results demonstrate that metformin induces Rab4 expression via AMPK‐AS160‐PKC‐zeta and modulates insulin‐mediated GLUT4 translocation. J. Cell. Physiol. 226: 974–981, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
959.
960.
Marbaix AY Noël G Detroux AM Vertommen D Van Schaftingen E Linster CL 《The Journal of biological chemistry》2011,286(48):41246-41252
The reduced forms of NAD and NADP, two major nucleotides playing a central role in metabolism, are continuously damaged by enzymatic or heat-dependent hydration. We report the molecular identification of the eukaryotic dehydratase that repairs these nucleotides and show that this enzyme (Carkd in mammals, YKL151C in yeast) catalyzes the dehydration of the S form of NADHX and NADPHX, at the expense of ATP, which is converted to ADP. Surprisingly, the Escherichia coli homolog, YjeF, a bidomain protein, catalyzes a similar reaction, but using ADP instead of ATP. The latter reaction is ascribable to the C-terminal domain of YjeF. This represents an unprecedented example of orthologous enzymes using either ADP or ATP as phosphoryl donor. We also show that eukaryotic proteins homologous to the N-terminal domain of YjeF (apolipoprotein A-1-binding protein (AIBP) in mammals, YNL200C in yeast) catalyze the epimerization of the S and R forms of NAD(P)HX, thereby allowing, in conjunction with the energy-dependent dehydratase, the repair of both epimers of NAD(P)HX. Both enzymes are very widespread in eukaryotes, prokaryotes, and archaea, which together with the ADP dependence of the dehydratase in some species indicates the ancient origin of this repair system. 相似文献