全文获取类型
收费全文 | 2710篇 |
免费 | 216篇 |
国内免费 | 1篇 |
出版年
2024年 | 6篇 |
2023年 | 23篇 |
2022年 | 48篇 |
2021年 | 102篇 |
2020年 | 47篇 |
2019年 | 73篇 |
2018年 | 72篇 |
2017年 | 69篇 |
2016年 | 110篇 |
2015年 | 179篇 |
2014年 | 182篇 |
2013年 | 209篇 |
2012年 | 259篇 |
2011年 | 200篇 |
2010年 | 145篇 |
2009年 | 119篇 |
2008年 | 146篇 |
2007年 | 143篇 |
2006年 | 140篇 |
2005年 | 124篇 |
2004年 | 96篇 |
2003年 | 87篇 |
2002年 | 86篇 |
2001年 | 15篇 |
2000年 | 14篇 |
1999年 | 18篇 |
1998年 | 12篇 |
1997年 | 9篇 |
1996年 | 10篇 |
1995年 | 15篇 |
1994年 | 11篇 |
1993年 | 9篇 |
1991年 | 11篇 |
1990年 | 7篇 |
1989年 | 6篇 |
1988年 | 13篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 15篇 |
1984年 | 9篇 |
1983年 | 8篇 |
1982年 | 9篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1973年 | 5篇 |
1967年 | 3篇 |
1962年 | 4篇 |
排序方式: 共有2927条查询结果,搜索用时 15 毫秒
31.
Cesare Peschle Maria Cristina Magli Clemente Cillo Federico Lettieri Francesco Pizzella Arturo Genovese Andrea Soricelli 《Life sciences》1977,21(6):773-778
A single administration of testosterone propionate (TP) in ex-hypoxic polycythemic mice induces, at 24 hr after androgen, an amplification of the erythroid burst-forming unit (BFU-E or B) pool in marrow. This phenomenon is not associated with an amplification of the erythroid colony-forming unit (CFU-E or E) compartment and is followed by its depletion. In the other hand, the 36–49 hr rise of erythropoietin (Ep) levels in serum is followed by a 60-hr amplification of the E pool. It is suggested that the latter phenomenon is mediated by enhanced Ep production, whereas the early amplification of the B compartment may derive from a direct influence of TP at the stem cell level. 相似文献
32.
M.Carmen Aragón Cecilio Giménez Federico Mayor Juan G. Marvizón Fernando Valdivieso 《生物化学与生物物理学报:生物膜》1981,646(3):465-470
Tyrosine uptake by membrane vesicles derived from rat brain has been investigated. The uptake is dependent on an Na+ gradient ([). The uptake is transport into an osmotically active space and not a binding artifact as indicated by the effect of increasing the medium osmolarity. The process is stimulated by a membrane potential (negative inside) as demonstrated by the effect of the ionophores valinomycin and carbonyl cyanide and anions with different permeabilities. Kinetic data show that tyrosine is accumulated by two systems with different affinities. Tyrosine uptake is inhibited by the presence of phenylalanine and tryptophan. 相似文献
33.
Photosynthetic fructose-1,6-diphosphatase (FDPase) fractions I and II, earlier purified from spinach leaves, show a similar amino acid composition, with the exception of a higher glutamic acid content in the latter. In both fractions glutamic and aspartic acids are the main amino acids. pH activity profiles of fractions I and II are similar, with optima at 8·65–8·70, both showing a high specificity for fructose- 1,6-diphosphate. These two fractions are Mg2+-dependent for activity, with an Optimum Mg2+ concentration of 10 mM in standard conditions, which shifts to 5 mM when the MG2+/EDTA ratio is increased to 10; Mn2+ and Co2+ are slightly active. EDTA enhances FDPase activity slightly, with an optimum at 0·4–0·8 mM. Cysteine has no activating effect, and acts as an inhibitor above 10 mM. Both I and II have an optimum substrate concentration of 4 mM, and the substrate inhibits at concns above this value. Kinetic velocity curves are sigmoidal, with the concave zone located in the range of physiological substrate concns. (Hill coefficient 1·75 for both). This suggests a strong regulatory role of fructose-1,6-diphosphate. Km values are 1·4 × 10−3 M (fraction I) and 1·1 × 10−3 M (fraction II). The highest activity rate occurs at 60°, in accordance with the high thermostability of both fractions; the activation energies are 14·3 kcal/mol (fraction I) and 13·0 kcal/mol (fraction II). 相似文献
34.
Federico Riu Roberta Ibba Stefano Zoroddu Simona Sestito Michele Lai Sandra Piras Luca Sanna Valentina Bordoni Luigi Bagella Antonio Carta 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):2223
Introduction: Colchicine-binding site inhibitors are some of the most interesting ligands belonging to the wider family of microtubule-destabilising agents.Results: A novel series of 4′-fluoro-substituted ligands (5–13) was synthesised. The antiproliferative activity assays resulted in nM values for the new benzotriazole-acrylonitrile derivatives. Compound 5, the hit compound, showed an evident blockade of HeLa cell cycle in the G2-M phase, but also a pro-apoptotic potential, and an increase of early and late apoptotic cells in HeLa and MCF-7 cell cycle analysis. Confocal microscopy analysis showed a segmented shape and a collapse of the cytoskeleton, as well as a consistent cell shrinkage after administration of 5 at 100 nM. Derivative 5 was also proved to compete with colchicine at colchicine-binding site, lowering its activity against tubulin polymerisation. In addition, co-administration of 5 and doxorubicin in drug-resistant A375 melanoma cell line highlighted a synergic potential in terms of inhibition of cell viability.Discussion: The 4′-fluoro substitution of benzotriazole-acrylonitrile scaffold brought us a step forward in the optimisation process to obtain compound 5 as promising MDA antiproliferative agent at nanomolar concentration. 相似文献
35.
Homeostasis of cell composition during prolonged darkness 总被引:1,自引:0,他引:1
The chemical composition of organisms in relation to their environmental resource availability is an area of intense research activity. We studied the changes in cell composition of the cyanobacterium Phormidium autumnale in response to prolonged darkness. Cells allocated their internal resources in a homeostatic manner, oxidizing all the three major cellular constituents in a proportional way. This resulted in constant C/N and carbohydrates, lipids and proteins ratios that remained unaltered throughout the whole incubation period. We propose the maintenance of balanced cell composition (homeostasis) as an evolutionary strategy related to environmental transitory changes. 相似文献
36.
El-Kabbani O Darmanin C Schneider TR Hazemann I Ruiz F Oka M Joachimiak A Schulze-Briese C Tomizaki T Mitschler A Podjarny A 《Proteins》2004,55(4):805-813
The X-ray structures of human aldose reductase holoenzyme in complex with the inhibitors Fidarestat (SNK-860) and Minalrestat (WAY-509) were determined at atomic resolutions of 0.92 A and 1.1 A, respectively. The hydantoin and succinimide moieties of the inhibitors interacted with the conserved anion-binding site located between the nicotinamide ring of the coenzyme and active site residues Tyr48, His110, and Trp111. Minalrestat's hydrophobic isoquinoline ring was bound in an adjacent pocket lined by residues Trp20, Phe122, and Trp219, with the bromo-fluorobenzyl group inside the "specificity" pocket. The interactions between Minalrestat's bromo-fluorobenzyl group and the enzyme include the stacking against the side-chain of Trp111 as well as hydrogen bonding distances with residues Leu300 and Thr113. The carbamoyl group in Fidarestat formed a hydrogen bond with the main-chain nitrogen atom of Leu300. The atomic resolution refinement allowed the positioning of hydrogen atoms and accurate determination of bond lengths of the inhibitors, coenzyme NADP+ and active-site residue His110. The 1'-position nitrogen atom in the hydantoin and succinimide moieties of Fidarestat and Minalrestat, respectively, form a hydrogen bond with the Nepsilon2 atom of His 110. For Fidarestat, the electron density indicated two possible positions for the H-atom in this bond. Furthermore, both native and anomalous difference maps indicated the replacement of a water molecule linked to His110 by a Cl-ion. These observations suggest a mechanism in which Fidarestat is bound protonated and becomes negatively charged by donating the proton to His110, which may have important implications on drug design. 相似文献
37.
Determination of diamine oxidase in lentil seedlings by enzymic activity and immunoreactivity
下载免费PDF全文
![点击此处可从《Plant physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A competitive radioimmunoassay for the quantitation of diamine oxidase (EC 1.4.3.6) from Lens culinaris is reported. Specific antibodies raised in rabbits immunized with a homogeneous preparation of the enzyme were incubated with purified 125I-enzyme and with either unlabeled diamine oxidase or plant material. Antigen-antibody complexes were isolated from the mixture by incubation with Staphylococcus protein A. The sensitivity of the test was about 5 nanograms in terms of enzyme protein. This assay was applied to the determination of the enzyme in extracts from lentil shoots grown either in the dark or in the light. Diamine oxidase activity and enzyme protein (as determined by radioimmunoassay) were measured during 7 days after germination. Both enzymic activity and enzyme protein declined slowly in the dark and rapidly in the light. These results indicate that fluctuation of the enzymic activity in this organ, both in the light and in the dark, are mediated via changes in the amount of the enzyme protein and not via the action of an inhibitor. 相似文献
38.
Mayor F Lucas E Jurado-Pueyo M Garcia-Guerra L Nieto-Vazquez I Vila-Bedmar R Fernández-Veledo S Murga C 《Archives of physiology and biochemistry》2011,117(3):125-130
G protein-coupled receptor kinase 2 (GRK2) is emerging as a key, integrative node in many signalling pathways. Besides its canonical role in the modulation of the signalling mediated by many G protein-coupled receptors (GPCR), this protein can display a very complex network of functional interactions with a variety of signal transduction partners, in a stimulus, cell type, or context-specific way. We review herein recent data showing that GRK2 can regulate insulin-triggered transduction cascades at different levels and that this protein plays a relevant role in insulin resistance and obesity in vivo, what uncovers GRK2 as a potential therapeutic target in the treatment of these disorders. 相似文献
39.