全文获取类型
收费全文 | 2309篇 |
免费 | 281篇 |
国内免费 | 4篇 |
出版年
2021年 | 27篇 |
2020年 | 25篇 |
2018年 | 23篇 |
2017年 | 23篇 |
2016年 | 41篇 |
2015年 | 61篇 |
2014年 | 61篇 |
2013年 | 85篇 |
2012年 | 108篇 |
2011年 | 98篇 |
2010年 | 62篇 |
2009年 | 59篇 |
2008年 | 68篇 |
2007年 | 74篇 |
2006年 | 76篇 |
2005年 | 77篇 |
2004年 | 67篇 |
2003年 | 85篇 |
2002年 | 63篇 |
2001年 | 74篇 |
2000年 | 54篇 |
1999年 | 71篇 |
1998年 | 39篇 |
1997年 | 27篇 |
1996年 | 36篇 |
1995年 | 31篇 |
1994年 | 32篇 |
1993年 | 26篇 |
1992年 | 48篇 |
1991年 | 48篇 |
1990年 | 38篇 |
1989年 | 53篇 |
1988年 | 36篇 |
1987年 | 33篇 |
1986年 | 34篇 |
1985年 | 35篇 |
1984年 | 33篇 |
1983年 | 24篇 |
1982年 | 31篇 |
1981年 | 27篇 |
1979年 | 42篇 |
1978年 | 42篇 |
1977年 | 32篇 |
1976年 | 33篇 |
1975年 | 29篇 |
1974年 | 42篇 |
1973年 | 39篇 |
1970年 | 23篇 |
1969年 | 28篇 |
1968年 | 29篇 |
排序方式: 共有2594条查询结果,搜索用时 15 毫秒
961.
Sharrow SD Edmonds KA Goodman MA Novotny MV Stone MJ 《Protein science : a publication of the Protein Society》2005,14(1):249-256
The mouse pheromones (+/-)-2-sec-butyl-4,5-dihydrothiazole (SBT) and 6-hydroxy-6-methyl-3-heptanone (HMH) bind into an occluded hydrophobic cavity in the mouse major urinary protein (MUP-1). Although the ligands are structurally unrelated, in both cases binding is accompanied by formation of a similar buried, water-mediated hydrogen bond network between the ligand and several backbone and side chain groups on the protein. To investigate the energetic contribution of this hydrogen bond network to ligand binding, we have applied isothermal titration calorimetry to measure the binding thermodynamics using several MUP mutants and ligand analogs. Mutation of Tyr-120 to Phe, which disrupts a hydrogen bond from the phenolic hydroxyl group of Tyr-120 to one of the bound water molecules, results in a substantial loss of favorable binding enthalpy, which is partially compensated by a favorable change in binding entropy. A similar thermodynamic effect was observed when the hydrogen bonded nitrogen atom of the heterocyclic ligand was replaced by a methyne group. Several other modifications of the protein or ligand had smaller effects on the binding thermodynamics. The data provide supporting evidence for the role of the hydrogen bond network in stabilizing the complex. 相似文献
962.
Liu FF Stone JR Schuldt AJ Okoshi K Okoshi MP Nakayama M Ho KK Manning WJ Marchionni MA Lorell BH Morgan JP Yan X 《American journal of physiology. Heart and circulatory physiology》2005,289(2):H660-H666
Neuregulins and their erbB receptors are essential for cardiac development and postulated to be cardioprotective in the presence of injury in the postnatal heart. We tested the hypothesis that the development of doxorubicin-induced cardiotoxicity in vivo is more severe in mice with heterozygous knockout of the neuregulin-1 gene (NRG-1(+/-)) compared with wild-type mice (WT). Three-month old NRG-1(+/-) and WT mice were injected with a single dose of doxorubicin (20 mg/kg ip). Survival was analyzed by the Kaplan-Meier approach. Left ventricular (LV) function and signaling pathways were analyzed 4 days after treatment. Fifteen days after treatment, survival was significantly lower in doxorubicin-treated NRG-1(+/-) mice (NRG-1(+/-)-Dox) compared with doxorubicin-treated WT mice (WT-Dox) (15% vs. 33%, P < 0.01). LV mass was significantly lower in NRG-1(+/-)-Dox but not in WT-Dox compared with nontreated animals. LV systolic pressure and LV midwall fractional shortening were significantly lower in NRG-1(+/-)-Dox compared with WT-Dox mice. LV protein levels of NRG-1, erbB2, and erbB4 receptors were similar in WT-Dox and NRG-1(+/-)-Dox mice. However, levels of phosphorylated erbB2, Akt, and ERK-1/2 were significantly decreased in NRG-1(+/-)-Dox compared with WT-Dox mice. A significant decrease in phosphorylated P70S6K levels was also observed in NRG-1(+/-)-Dox compared with nontreated NRG-1(+/-) mice. These results demonstrate that heterozygous knockout of the neuregulin-1 gene worsens survival and LV function in the presence of doxorubicin-induced cardiac injury in vivo. This is associated with the depression of activation of the erbB2 receptor as well as Akt, p70S6K, and ERK-1/2 pathways. 相似文献
963.
Shi SD Greig MJ Solowiej JE Murray BW 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,825(2):176-185
Liquid chromatography-mass spectrometry (LC-MS) has been used extensively in determination of the molecular weights of proteins, as well as covalent protein-ligand complexes. We have successfully developed LC-MS method for protein molecular weight measurement using small-bore and capillary LC-MS under acidic and basic conditions. A high pH method was critical in studying complexes that were unstable under acidic conditions. Microgram sensitivity was achieved using both methods. A protocol to study the binding mode of protein-ligand complexes under denaturing conditions was developed. These methods were applied to CP88 (a proprietary cysteine protease) inhibitors and revealed different binding modes of inhibitors to proteins that had similar non-reversible behavior in biochemical activity assays. The method also confirmed that one inhibitor studied binds to CP88 in a reversible covalent manner. 相似文献
964.
965.
966.
967.
1. A beta-(1-->4)-glucan hydrolase prepared from Aspergillus niger, as described by Clarke & Stone (1965a), showed a pH optimum in the range 4.5-6 and K(m) 0.25% when acting on a cellulose dextrin sulphate substrate. 2. The hydrolase rapidly decreased the specific viscosity of carboxymethylcellulose with a small increase in the production of reducing sugars. The identity of the products of hydrolysis of cellotetraose, cellopentaose and their reduced analogues indicate a preferential cleavage of non-terminal glucosidic linkages. The enzyme may be described as beta-(1-->4)-glucan 4-glucanohydrolase (EC 3.2.1.4). 3. In addition to carboxymethylcellulose, cellulose dextrins, cellopentaose and cellotetraose the enzyme fraction hydrolysed lichenin, oat and barley glucans, ivory-nut mannan and a glucomannan from Konjak flour. No hydrolysis of wheat-straw beta-(1-->4)-xylan, Lupinus albus beta-(1-->4)-galactan, pneumococcal type III polysaccharide, chitin, hyaluronic acid, laminarin, pachydextrins, carboxymethylpachyman or beta-(1-->3)-oligoglucosides was detected. 4. The hydrolase showed no transglycosylase activity from cellodextrin or cellopentaose substrates to glucose or methanol acceptors. 5. The hydrolysis of cellodextrins was inhibited completely by 1.0mm-Hg(2+), 0.7mm-phenylmercuric nitrate and 1.0mm-iodine. 相似文献
968.
A complex porphyrin which has not been hitherto described is found in liquid cultures of C. diphtheriae. The porphyrin is a combination of coproporphyrin with both iron and copper, and shows an oxidation-reduction change. This is the first report, as far as we are able to determine, of a porphyrin compound which contains both iron and copper in its molecule. Its source is in all probability the cytochome of the bacilli.
The content of porphyrin is proportional to the biological titer of the culture filtrate; the suggestion is offered that the toxin itself is derived from cytochrome. 相似文献
969.
CELL DIVISION AND DNA SYNTHESIS IN TETRAHYMENA PYRIFORMIS DEPRIVED OF ESSENTIAL AMINO ACIDS 总被引:8,自引:6,他引:2 下载免费PDF全文
The question of amino acid requirements for DNA synthesis and cell division has been studied in Tetrahymena pyriformis by depriving cells of histidine and tryptophan at defined stages in the interdivision interval. Deprivation any time before DNA synthesis does not prevent the initiation of such synthesis but completely inhibits the following division and limits the increase in DNA, as measured microspectrophotometrically, to 20 per cent. H3-thymidine added to the medium is not incorporated during the 20 per cent increase. Deprivation after DNA synthesis is initiated does not prevent the continuation (to completion) of DNA synthesis, and cell division ensues. H3-thymidine added to the medium under these conditions is incorporated into macronuclear DNA. The data indicate that some amino acid-dependent event occurs, about the time of the beginning of the DNA synthesis period, which is not essential for initiation of DNA synthesis but which is essential for the maintenance of synthesis once it has begun. These results are further discussed in terms of enzymes required to convert thymidine (and possibly the other three deoxyribonucleosides) to the immediate precursor of DNA synthesis. 相似文献
970.