全文获取类型
收费全文 | 811篇 |
免费 | 112篇 |
国内免费 | 2篇 |
出版年
2022年 | 8篇 |
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 14篇 |
2018年 | 14篇 |
2017年 | 17篇 |
2016年 | 19篇 |
2015年 | 37篇 |
2014年 | 36篇 |
2013年 | 31篇 |
2012年 | 65篇 |
2011年 | 53篇 |
2010年 | 38篇 |
2009年 | 35篇 |
2008年 | 43篇 |
2007年 | 45篇 |
2006年 | 44篇 |
2005年 | 55篇 |
2004年 | 62篇 |
2003年 | 46篇 |
2002年 | 38篇 |
2001年 | 8篇 |
2000年 | 13篇 |
1999年 | 18篇 |
1998年 | 9篇 |
1997年 | 9篇 |
1996年 | 12篇 |
1995年 | 6篇 |
1994年 | 14篇 |
1993年 | 9篇 |
1992年 | 13篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 14篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 9篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 7篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1961年 | 2篇 |
排序方式: 共有925条查询结果,搜索用时 15 毫秒
11.
We examined the interaction of glycolipid-containing phospholipid vesicles with rat hepatocytes in vitro. Incorporation of either or the monosialoganglioside, GM1, enhanced liposomal lipid uptake 4–5-fold as judged by the uptake of radioactive phosphatidylcholine as a vesicle marker. Cerebroside enhanced phospholipid uptake only when incorporated into dimyristoyl, but not into egg phosphatidylcholine vesicles. The lack of cerebroside effect in egg phosphatidylcholine-containing vesicles appeared to be due to a limited exposure of the carbohydrate part of the glycolipid as suggested by the reduced agglutinability of those vesicles by Ricinus communis agglutinin.In contrast to the results with radioactive phosphatidylcholine, we observed only a 20% increase in vesicle-cell association as a result of glycolipid incorporation, when a trace amount of [14C]cholesteryloleate served as a marker of the liposomal lipids or when using the fluorescent dye, carboxyfluorescein, as a marker of the aqueous space of the vesicles. By the same token, intracellular delivery of vesicle-contents was only slightly enhanced (approx. 10%).The discrepancy between the association with the cells of phosphatidylcholine on the one hand and cholesteryoleate or entrapped marker on the other suggests different mechanisms of uptake for these markers. Our results are compatible with the notion that the main effect of incorporation of glycolipids into the vesicles is the enhancement of exchange or transfer of phospholipid molecules between vesicles and cells. Incubation of the cells with galactose or lactose, prior to addition of vesicles, suggests that this enhanced phospholipid exchange or transfer involves specific recognition of the terminal galactose residues of the glycolipid vesicles by a receptor present on the plasma membranes of hepatocytes. 相似文献
12.
Johannis P. Kamerling Gerrit J. Gerwig Johannes F.G. Vliegenthart Marinus Duran Dirk Ketting Sybe K. Wadman 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1977,143(2):117-123
The separation of the enantiomers of lactic and glyceric acids can be achieved by capillary gas chromatography on SP-1000 using the corresponding O-acetylated menthyl esters. The structures of the derivatives were proved by proton magnetic resonance spectroscopy and mass spectrometry. The method has been used for the determination of the absolute configurations of lactic and glyceric acids isolated from serum and urine from different patients. 相似文献
13.
In petals of Silene dioica, gene P controls the 3′-hydroxylation of the anthocyanin B-ring and the hydroxylation pattern of the hydroxycinnamoyl acyl group bound to the 4″'-hydroxyl group of rhamnose of anthocyanidin 3-rhamnosyl(1→6)glucoside-5-glucoside. In this paper, experiments are presented which show that gene P is involved in the hydroxylation of p-coumaroyl-CoA to caffeoyl-CoA, which is then used both as a precursor in anthocyanin biosynthesis and as a substrate for the final acylation. 相似文献
14.
John Kamsteeg Jan van Brederode Gerrit van Nigtevecht 《Biochemical genetics》1978,16(11-12):1045-1058
An enzyme catalyzing the transfer of the glucosyl moiety of UDP-glucose to the 3-hydroxyl group of cyanidin has been demonstrated in petal extracts of Silene dioica mutants with cyanidin-3-O-glucoside in the petals. This transferase activity was also present in young rosette leaves and calyces of these plants. The highest glucosyltransferase activity was found in petals of opening flowers of young plants. The enzyme was purified ninetyfold by PVP and Sephadex chromatography. The glucosyltransferase had a pH optimum of 7.5, had a “true Km value” of 4.1×10?4 m for UDP-glucose and 0.4×10?4 m for cyanidin chloride, and was not stimulated by divalent metal ions. Both p-chloromercuribenzoate and HgCl2 inhibited the enzyme activity. Pelargonidin chloride and delphinidin chloride at reduced rates also served as substrates. The enzyme did not catalyze the glucosylation of the 3-hydroxyl group of flavonols or the 5-hydroxyl group of anthocyanins. ADP-glucose could not serve as a glucosyl donor. The results of Sephadex G150 chromatography suggest that the glucosyltransferase can exist as dimer of about 125,000 daltons and as active monomers of 60,000 daltons. The genetic control of the glucosyltransferase activity is discussed. 相似文献
15.
de Swaaf ME de Rijk TC van der Meer P Eggink G Sijtsma L 《Journal of biotechnology》2003,103(1):21-29
The lipids of the heterotrophic microalga Crypthecodinium cohnii contain the omega-3 polyunsaturated fatty acid (PUFA) and docosahexaenoic acid (22:6) to a level of over 30%. The pathway of 22:6 synthesis in C. cohnii is unknown. The ability of C. cohnii to use 13C-labelled externally supplied precursor molecules for 22:6 biosynthesis was tested by 13C NMR analysis. Furthermore, the presence of desaturases (typical for aerobic PUFA synthesis) was studied by the addition of specific desaturase inhibitors in the growth medium. The addition of 1-(13)C acetate or 1-(13)C butyrate in the growth medium resulted in 22:6 with only the odd carbon atoms enriched. Apparently, two-carbon units were used as building blocks for 22:6 synthesis and butyrate was first split into two-carbon units prior to incorporation in 22:6. When 1-(13)C oleic acid was added to the growth medium, 1-(13)C oleic acid was incorporated into the lipids of C. cohnii but was not used as a precursor for the synthesis of 22:6. Specific desaturase inhibitors (norflurazon and propyl gallate) inhibited lipid accumulation in C. cohnii. The fatty acid profile, however, was not altered. In contrast, in the arachidonic acid-producing fungus, Mortierella alpina, these inhibitors not only decreased the lipid content but also altered the fatty acid profile. Our results can be explained by the presence of three tightly regulated separate systems for the fatty acid production by C. cohnii, namely for (1). the biosynthesis of saturated fatty acids, (2). the conversion of saturated fatty acids to monounsaturated fatty acids and (3). the de novo synthesis of 22:6 with desaturases involved. 相似文献
16.
Hennecke G Nolte J Volkmer-Engert R Schneider-Mergener J Behrens S 《The Journal of biological chemistry》2005,280(25):23540-23548
The Escherichia coli periplasmic chaperone and peptidyl-prolyl isomerase (PPIase) SurA facilitates the maturation of outer membrane porins. Although the PPIase activity exhibited by one of its two parvulin-like domains is dispensable for this function, the chaperone activity residing in the non-PPIase regions of SurA, a sizable N-terminal domain and a short C-terminal tail, is essential. Unlike most cytoplasmic chaperones SurA is selective for particular substrates and recognizes outer membrane porins synthesized in vitro much more efficiently than other proteins. Thus, SurA may be specialized for the maturation of outer membrane proteins. We have characterized the substrate specificity of SurA based on its natural, biologically relevant substrates by screening cellulose-bound peptide libraries representing outer membrane proteins. We show that two features are critical for peptide binding by SurA: specific patterns of aromatic residues and the orientation of their side chains, which are found more frequently in integral outer membrane proteins than in other proteins. For the first time this sufficiently explains the capability of SurA to discriminate between outer membrane protein and non-outer membrane protein folding intermediates. Furthermore, peptide binding by SurA requires neither an active PPIase domain nor the presence of proline, indicating that the observed substrate specificity relates to the chaperone function of SurA. Finally, we show that SurA is capable of associating with the outer membrane. Together, our data support a model in which SurA is specialized to interact with non-native periplasmic outer membrane protein folding intermediates and to assist in their maturation from early to late outer membrane-associated steps. 相似文献
17.
18.
Júlia R. de Rezende Thomas B. P. Oldenburg Tetyana Korin William D. L. Richardson Milovan Fustic Carolyn M. Aitken Bernard F. J. Bowler Angela Sherry Alexander Grigoryan Gerrit Voordouw Stephen R. Larter Ian M. Head Casey R. J. Hubert 《Environmental microbiology》2020,22(8):3049-3065
Most of the oil in low temperature, non-uplifted reservoirs is biodegraded due to millions of years of microbial activity, including via methanogenesis from crude oil. To evaluate stimulating additional methanogenesis in already heavily biodegraded oil reservoirs, oil sands samples were amended with nutrients and electron acceptors, but oil sands bitumen was the only organic substrate. Methane production was monitored for over 3000 days. Methanogenesis was observed in duplicate microcosms that were unamended, amended with sulfate or that were initially oxic, however methanogenesis was not observed in nitrate-amended controls. The highest rate of methane production was 0.15 μmol CH4 g−1 oil d−1, orders of magnitude lower than other reports of methanogenesis from lighter crude oils. Methanogenic Archaea and several potential syntrophic bacterial partners were detected following the incubations. GC–MS and FTICR–MS revealed no significant bitumen alteration for any specific compound or compound class, suggesting that the very slow methanogenesis observed was coupled to bitumen biodegradation in an unspecific manner. After 3000 days, methanogenic communities were amended with benzoate resulting in methanogenesis rates that were 110-fold greater. This suggests that oil-to-methane conversion is limited by the recalcitrant nature of oil sands bitumen, not the microbial communities resident in heavy oil reservoirs. 相似文献
19.
Sanne R. Martens-de Kemp Arjen Brink Marijke Stigter-van Walsum J. Mirjam A. Damen François Rustenburg Thijs Wu Wessel N. van Wieringen Gerrit Jan Schuurhuis Boudewijn J.M. Braakhuis Monique Slijper Ruud H. Brakenhoff 《Stem cell research》2013,10(3):477-488
Patients with advanced head and neck squamous cell carcinomas (HNSCCs) are often treated with concomitant chemotherapy and radiotherapy, but only 50% is cured. A possible explanation for treatment failure is therapy resistance of the cancer stem cells (CSCs). The application of compounds specifically targeting these CSCs, in addition to routinely used therapeutics, would likely improve clinical outcome. We demonstrate that the previously described monoclonal antibody K984 recognizes the CD98 cell surface protein, which is specifically expressed by cells forming the squamous basal cell layer, the region where the squamous stem cells reside. Moreover, CD98 is highly resistant to the proteolytic enzymes required for CSC enrichment procedures. We show that CD98high cells, in contrast to CD98low cells, are able to generate tumors in immunodeficient mice, indicating that CD98high cells have stem cell characteristics. Furthermore, the CD98high subpopulation expresses high levels of cell cycle control and DNA repair genes, while the CD98low fraction shows expression patterns that represent the more differentiated cells forming the bulk of the tumor. CD98 is a promising CSC enrichment marker in HNSCC. Our data support the CSC concept in head and neck cancer and the potential relevance of these cells for treatment outcome. 相似文献
20.
Kevin D. Shield Gerrit Gmel Tara Kehoe-Chan Deborah A. Dawson Bridget F. Grant Jürgen Rehm 《PloS one》2013,8(1)