全文获取类型
收费全文 | 2163篇 |
免费 | 134篇 |
出版年
2024年 | 7篇 |
2023年 | 19篇 |
2022年 | 32篇 |
2021年 | 57篇 |
2020年 | 29篇 |
2019年 | 42篇 |
2018年 | 62篇 |
2017年 | 49篇 |
2016年 | 65篇 |
2015年 | 103篇 |
2014年 | 99篇 |
2013年 | 150篇 |
2012年 | 185篇 |
2011年 | 154篇 |
2010年 | 111篇 |
2009年 | 96篇 |
2008年 | 148篇 |
2007年 | 131篇 |
2006年 | 114篇 |
2005年 | 120篇 |
2004年 | 83篇 |
2003年 | 74篇 |
2002年 | 82篇 |
2001年 | 29篇 |
2000年 | 23篇 |
1999年 | 18篇 |
1998年 | 31篇 |
1997年 | 14篇 |
1996年 | 13篇 |
1995年 | 14篇 |
1994年 | 8篇 |
1993年 | 9篇 |
1992年 | 13篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 11篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1969年 | 1篇 |
排序方式: 共有2297条查询结果,搜索用时 15 毫秒
181.
Biftu T Feng D Qian X Liang GB Kieczykowski G Eiermann G He H Leiting B Lyons K Petrov A Sinha-Roy R Zhang B Scapin G Patel S Gao YD Singh S Wu J Zhang X Thornberry NA Weber AE 《Bioorganic & medicinal chemistry letters》2007,17(1):49-52
Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin. 相似文献
182.
Biotechnological conversion of agro-industrial wastewaters into biodegradable plastic, poly beta-hydroxybutyrate 总被引:1,自引:0,他引:1
Khardenavis AA Suresh Kumar M Mudliar SN Chakrabarti T 《Bioresource technology》2007,98(18):3579-3584
Waste activated sludge generated from a combined dairy and food processing industry wastewater treatment plant was evaluated for its potential to produce biodegradable plastic, poly beta-hydroxybutyric acid (PHB). Deproteinized jowar grain-based distillery spentwash yielded 42.3% PHB production (w/w), followed by filtered rice grain-based distillery spentwash (40% PHB) when used as substrates. Addition of di-ammonium hydrogen phosphate (DAHP) resulted in an increase in PHB production to 67% when raw rice grain-based spentwash was used. Same wastewater, after removal of suspended solids by filtration and with DAHP supplementation resulted in lower PHB production (57.9%). However, supplementing other wastes with DAHP led to a substantial decrease in PHB content in comparison to what was observed in the absence of DAHP. 相似文献
183.
Biftu T Scapin G Singh S Feng D Becker JW Eiermann G He H Lyons K Patel S Petrov A Sinha-Roy R Zhang B Wu J Zhang X Doss GA Thornberry NA Weber AE 《Bioorganic & medicinal chemistry letters》2007,17(12):3384-3387
Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo activity and pharmacokinetic profile. 相似文献
184.
The requirement of sterol glucoside for pexophagy in yeast is dependent on the species and nature of peroxisome inducers
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nazarko TY Polupanov AS Manjithaya RR Subramani S Sibirny AA 《Molecular biology of the cell》2007,18(1):106-118
Sterol glucosyltransferase, Ugt51/Atg26, is essential for both micropexophagy and macropexophagy of methanol-induced peroxisomes in Pichia pastoris. However, the role of this protein in pexophagy in other yeast remained unclear. We show that oleate- and amine-induced peroxisomes in Yarrowia lipolytica are degraded by Atg26-independent macropexophagy. Surprisingly, Atg26 was also not essential for macropexophagy of oleate- and amine-induced peroxisomes in P. pastoris, suggesting that the function of sterol glucoside (SG) in pexophagy is both species and peroxisome inducer specific. However, the rates of degradation of oleate- and amine-induced peroxisomes in P. pastoris were reduced in the absence of SG, indicating that P. pastoris specifically uses sterol conversion by Atg26 to enhance selective degradation of peroxisomes. However, methanol-induced peroxisomes apparently have lost the redundant ability to be degraded without SG. We also show that the P. pastoris Vac8 armadillo repeat protein is not essential for macropexophagy of methanol-, oleate-, or amine-induced peroxisomes, which makes PpVac8 the first known protein required for the micropexophagy, but not for the macropexophagy, machinery. The uniqueness of Atg26 and Vac8 functions under different pexophagy conditions demonstrates that not only pexophagy inducers, such as glucose or ethanol, but also the inducers of peroxisomes, such as methanol, oleate, or primary amines, determine the requirements for subsequent pexophagy in yeast. 相似文献
185.
Cystathionine-beta-synthase gene transfer and 3-deazaadenosine ameliorate inflammatory response in endothelial cells 总被引:1,自引:0,他引:1
Sen U Tyagi N Kumar M Moshal KS Rodriguez WE Tyagi SC 《American journal of physiology. Cell physiology》2007,293(6):C1779-C1787
Although elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) are associated with increased inflammation and vascular remodeling, the mechanism of Hcy-mediated inflammation and vascular remodeling is unclear. The matrix metalloproteinases (MMPs) and adhesion molecules play an important role in vascular remodeling. We hypothesized that HHcy induces inflammation by increasing adhesion molecules and matrix protein expression. Endothelial cells were supplemented with high methionine, and Hcy accumulation was measured by HPLC. Nitric oxide (NO) bioavailability was detected by a NO probe. The protein expression was measured by Western blot analysis. MMP-9 activity was detected by gelatin-gel zymography. We demonstrated that methionine supplement promoted upregulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) through increased Hcy accumulation. In addition, increased synthesis of collagen type-1 was also observed. MMP-9 gene expression and protein activity were increased in methionine supplement groups. 3-Deazaadenosine (DZA), an adenosine analogue, prevented high methionine-induced ICAM-1 and VCAM-1 expression and collagen type-1 synthesis. Transfection of endothelial cells with cystathionine-beta-synthase (CBS) gene construct, which converts Hcy to cystathionine, reduced Hcy accumulation in high methionine-fed cells. CBS gene transfection reduced the inflammatory response, as evident by attenuated ICAM-1 and VCAM-1 expression. Furthermore, collagen type-1 expression and MMP-9 activity were dramatically attenuated with CBS gene transfection. These results suggested that methionine supplement increased Hcy accumulation, which was associated with inflammatory response and matrix remodeling such as collagen type-1 synthesis and MMP-9 activity. However, in vitro DZA and CBS gene therapy successfully treated the HHcy-induced inflammatory reaction in the methionine metabolism pathway. 相似文献
186.
Lind H Sjögren J Gohil S Kenne L Schnürer J Broberg A 《FEMS microbiology letters》2007,271(2):310-315
Antifungal compounds from cultures of five type strains of dairy propionibacteria, as well as from the cultivation medium, were studied. Cell-free supernatants and medium were fractionated by C(18) solid phase extraction. The aqueous 95% acetonitrile fractions were analyzed by GC-MS or subjected to reversed-phase HPLC, to identify, quantify or isolate antifungal substances. The resulting HPLC fractions were screened for antifungal activity against the mold Aspergillus fumigatus and the yeast Rhodotorula mucilaginosa. Active fractions were further separated by HPLC and the structures of the compounds were determined by spectroscopic and chromatographic methods. All five strains produced 3-phenyllactic acid, at concentrations ranging from 1.0 microg mL(-1) (Propionibacterium freudenreichii ssp. shermanii) to 15.1 microg mL(-1) (Propionibacterium thoenii), and at L/D -ratios ranging from 2 : 3 (Propionibacterium acidipropionici) to 9 : 1 (Propionibacterium freudenreichii). A number of active compounds found in cultures of propionibacteria were also present in noninoculated growth medium: two antifungal diketopiperazines, cyclo(L-Phe-L-Pro) and cyclo(L-Ile-L-Pro), and seven antifungal linear peptides. Three of the linear peptides corresponded to sequences found in the medium component casein, suggesting their origin from this component, whereas the diketopiperazines were suggested to be formed from medium peptides by heat treatment. 相似文献
187.
188.
Stensvold CR Suresh GK Tan KS Thompson RC Traub RJ Viscogliosi E Yoshikawa H Clark CG 《Trends in parasitology》2007,23(3):93-96
Blastocystis is a ubiquitous enteric protistan parasite that has extensive genetic diversity and infects humans and many other animals. Distinct molecular methodologies developed to detect variation and obtain information about transmission patterns and clinical importance have resulted in a confusing array of terminologies for the identification and designation of Blastocystis subtypes. In this article, we propose a standardization of Blastocystis terminology to improve communication and correlate research results. Based primarily on published small-subunit ribosomal RNA gene analyses, we propose that all mammalian and avian isolates should be designated Blastocystis sp. and assigned to one of nine subtypes. 相似文献
189.
The purpose of this research was to study whether the bioavailability of lovastatin could be improved by administering lovastatin
solid lipid nanoparticles (SLN) duodenally to rats. Lovastatin SLN were developed using triglycerides by hot homogenization
followed by ultrasonication. Particle size and zeta potential were measured by photon correlation spectroscopy. The solid
state of the drug in the SLN and lipid modification were characterized. Bioavailability studies were conducted in male Wistar
rats after intraduodenal administration of lovastatin suspension and SLN. Stable lovastatin SLN having a mean size range of
60 to 119 nm and a zeta potential range of −16 to −21 mV were developed. More than 99% of the lovastatin was entrapped in
the SLN. Lovastatin was dispersed in an amorphous state, and triglycerides were in {ieE162-1} form in the SLN. In vitro stability
studies showed the slow release and stability of lovastatin SLN. The relative bioavailabilities of lovastatin and lovastatin
hydroxy acid of SLN were increased by ∼173% and 324%, respectively, compared with the reference lovastatin suspension.
Published: March 23, 2007 相似文献
190.
Paul Prajita Patel Paritosh Verma Suresh K. Mishra Pragyan Sahu Bikash R. Panda Pritam Kumar Kushwaha Gajraj Singh Senapati Shantibhusan Misra Namrata Suar Mrutyunjay 《Cell biology and toxicology》2022,38(1):111-127
Cell Biology and Toxicology - The key to bacterial virulence relies on an exquisite balance of signals between microbe and hosts. Bacterial toxin–antitoxin (TA) system is known to play a... 相似文献