全文获取类型
收费全文 | 3692篇 |
免费 | 282篇 |
国内免费 | 207篇 |
出版年
2023年 | 69篇 |
2022年 | 111篇 |
2021年 | 91篇 |
2020年 | 86篇 |
2019年 | 109篇 |
2018年 | 130篇 |
2017年 | 108篇 |
2016年 | 89篇 |
2015年 | 94篇 |
2014年 | 257篇 |
2013年 | 280篇 |
2012年 | 185篇 |
2011年 | 233篇 |
2010年 | 174篇 |
2009年 | 194篇 |
2008年 | 202篇 |
2007年 | 242篇 |
2006年 | 155篇 |
2005年 | 127篇 |
2004年 | 91篇 |
2003年 | 77篇 |
2002年 | 46篇 |
2001年 | 30篇 |
2000年 | 43篇 |
1999年 | 52篇 |
1998年 | 42篇 |
1997年 | 41篇 |
1996年 | 42篇 |
1995年 | 37篇 |
1994年 | 37篇 |
1993年 | 53篇 |
1992年 | 42篇 |
1991年 | 33篇 |
1990年 | 28篇 |
1989年 | 23篇 |
1988年 | 24篇 |
1987年 | 30篇 |
1986年 | 25篇 |
1985年 | 34篇 |
1984年 | 50篇 |
1983年 | 41篇 |
1982年 | 46篇 |
1981年 | 35篇 |
1980年 | 48篇 |
1979年 | 42篇 |
1978年 | 26篇 |
1977年 | 26篇 |
1976年 | 17篇 |
1974年 | 22篇 |
1973年 | 20篇 |
排序方式: 共有4181条查询结果,搜索用时 15 毫秒
11.
《Bioorganic & medicinal chemistry letters》2014,24(6):1523-1527
The non-receptor tyrosine kinase Syk (spleen tyrosine kinase) is a pharmaceutical relevant target because its over-activation is observed in several autoimmune diseases, allergy, and asthma. Here we report the identification of two novel inhibitors of Syk by high-throughput docking into a rare C-helix-out conformation published recently. Interestingly, both compounds are slightly more active on ZAP70 (Zeta-chain-associated protein kinase 70), which is the kinase closest to Syk in the phylogenetic tree of human kinases. Taken together, the docking pose and experimental results suggest that the higher affinity of the inhibitors for ZAP70 than Syk originates from a more populated C-helix-out conformation in ZAP70. The latter observation is congruent with the 100-fold lower intrinsic activity of ZAP70 than Syk, as the C-helix-out conformation is inactive. The pharmacophore features of DFG-in, C-helix-out compounds are analyzed in relation to DFG-out inhibitors. 相似文献
12.
《Molecular & cellular proteomics : MCP》2023,22(2):100490
Aspergillus flavus is a common saprophytic and pathogenic fungus, and its secondary metabolic pathways are one of the most highly characterized owing to its aflatoxin (AF) metabolite affecting global economic crops and human health. Different natural environments can cause significant variations in AF synthesis. Succinylation was recently identified as one of the most critical regulatory post-translational modifications affecting metabolic pathways. It is primarily reported in human cells and bacteria with few studies on fungi. Proteomic quantification of lysine succinylation (Ksuc) exploring its potential involvement in secondary metabolism regulation (including AF production) has not been performed under natural conditions in A. flavus. In this study, a quantification method was performed based on tandem mass tag labeling and antibody-based affinity enrichment of succinylated peptides via high accuracy nano-liquid chromatography with tandem mass spectrometry to explore the succinylation mechanism affecting the pathogenicity of naturally isolated A. flavus strains with varying toxin production. Altogether, 1240 Ksuc sites in 768 proteins were identified with 1103 sites in 685 proteins quantified. Comparing succinylated protein levels between high and low AF-producing A. flavus strains, bioinformatics analysis indicated that most succinylated proteins located in the AF biosynthetic pathway were downregulated, which directly affected AF synthesis. Versicolorin B synthase is a key catalytic enzyme for heterochrome B synthesis during AF synthesis. Site-directed mutagenesis and biochemical studies revealed that versicolorin B synthase succinylation is an important regulatory mechanism affecting sclerotia development and AF biosynthesis in A. flavus. In summary, our quantitative study of the lysine succinylome in high/low AF-producing strains revealed the role of Ksuc in regulating AF biosynthesis. We revealed novel insights into the metabolism of AF biosynthesis using naturally isolated A. flavus strains and identified a rich source of metabolism-related enzymes regulated by succinylation. 相似文献
13.
14.
《Redox report : communications in free radical research》2013,18(5):234-237
AbstractThe role of hemoglobin in transporting oxygen is dependent on the reversible binding of oxygen to Fe(II) hemoglobin with molecular oxygen released at reduced oxygen pressures. The partially oxygenated hemoglobin formed with the release of oxygen from hemoglobin is susceptible to redox reactions where the functional Fe(II) heme is oxidized to Fe(III) and the substrate is reduced. In this article, we review two important redox reactions of hemoglobin and discuss the ramifications of these reactions. The reduction of oxygen to superoxide starts a cascade of oxidative reactions, which are a source for red cell-induced oxidative stress. The reduction of nitrite to nitric oxide produces a labile form of nitric oxide that can be a source for oxidative stress, but can also have important physiological functions. 相似文献
15.
G E Brown S A Fischkoff J V Ordonez 《Biochemical and biophysical research communications》1984,123(3):937-943
The ability of a myeloid leukemia cell line (HL-60) to undergo membrane electrical potential changes was followed during neutrophilic differentiation induced by 2 compounds. Membrane-potential changes were induced with 12-O-tetradecanoylphorbol 13-acetate (TPA) or formyl-methionyl-leucyl-phenylalanine (FMLP) and were monitored by flow cytometry. The magnitude of the membrane-potential response to TPA increased in a more uniform manner as the population of cells matured than did acquisition of mature morphology or ability to undergo the respiratory burst in response to TPA. The response to TPA and FMLP of HL-60 cells, maximally induced to differentiate by dimethylsulfoxide, closely resembled that of neutrophils. Thus, HL-60 cells may be a useful tool in the study of the relation between membrane depolarization and subsequent cellular activation. 相似文献
16.
The growth response ofCalopogonium caeruleum, a leguminous covercrop in plantation agriculture, to inoculation with two vesicular-arbuscular mycorrhizal (VAM) fungi was
investigated in five phosphorus (P)-deficient soils supplied with various levels of rock phosphate. Significant shoot yield
increases over the uninoculated controls were obtained in most sterilised or unsterilised soils at all applied P levels, although
the inoculant VAM fungi differed in their effectiveness in the soils used. Responses in mycorrhizal root infections, P and
nitrogen (N) concentrations in tops and plant nodulation varied. The results are discussed in relation to the edaphic environment
of the mycorrhizal association. 相似文献
17.
David T. Osuga Milton S. Feather Mena J. Shah Robert E. Feeney 《Journal of Protein Chemistry》1989,8(4):519-528
Amino acids and peptides have been attached to the C-6 hydroxyls of the galactose and the N-acetylgalactosamine by first oxidizing the C-6 hydroxyls to the aldehydes by galactose oxidase in the presence of small amounts of catalase, followed by reductive amination (-amino group) in the presence of cyanoborohydride. The activity of oxidized antifreeze glycoprotein was >70% of the original, and considerable activity has been retained with some substitutions on reductive amination using cyanoborohydride. The following were some activities retained (as compared with the oxidized antifreeze glycoprotein): Gly, 64; (Gly)2, 88; (Gly)3, 82; (Gly)4, 70; Gly-Gly-NH2, 44, Gly-Glu, 13; Gly-Leu, 40; Gly-Tyr, 57; Gly-Gly-Leu, 50; Gly-Gly-Phe, 30; and Gly-Gly-Val, 35. On amino acid analysis of acid hydrolysates, some release of the amino acid attached by amination occurred; e.g., Gly-Tyr gave 0.26 Gly and 0.49 Tyr per disaccharide. 相似文献
18.
The effect of tin and lead on levels of essential metals (Zn, Cu, Ca, Fe) in rabbit tissues was compared in relation to the route of administration. Animals received intraperitoneally, or per os, SnCl2 (2 mg Sn/kg) or Pb(CH3COO)2 (3.5 mg Pb/kg) every day for 5 d or for 1 mo. Copper, zinc, iron, and calcium were determined by AAS in the liver, kidneys, spleen, brain, bone marrow, and blood; lead and tin concentration were measured in the blood of animals. Tin and lead administered per os caused either no changes or the decreased concentration of endogenous metals in several tissues. The other route of administration (ip) of both metals generally contributed to the increased storage of essential elements. Blood tin levels of tin treated animals were only about less than or equal to 1/10 of blood lead concentrations of rabbits exposed to lead. 相似文献
19.
Kunio Yonemasu Takako Sasaki Yoshiko Dohi Charles M. Lapière Betty Nusgens 《生物化学与生物物理学报:疾病的分子基础》1990,1096(1):47-51
C1q, a collagen-like complement protein, was purified from the serum of a ddermatosparactic calf which lacks procollagen N-terminal proteinase (pN-proteinase). The specific hemolytic activity of the serum Clq from the dermatosparactic animal was identical to that of C1q from a normal calf. Gel-filtration of serum from dermatosparactic calf, on Sepharose 6B, showed the presence of C1q-antigenic material at only one position which was identical to the elution position of normal bovine C1q. No differdence, under dissociating conditions, could be seen in the size of the chains of C1q in specific immunoprecipitates isolated from the sera of dermatosparactic and normal animals, as judged by polyacrylamidegel electrophoresis (PAGE) in the presence of sodium dodecyl sulfate (SDS). The C1q from the dermatosparactic animal showed the same N-terminal amino acid and typtic-digest peptide pattern on HPLC as C1q from the normal calf. These results strongly suggest that pN-proteinase is not involved in the extracellular processing of C1q. 相似文献
20.
Hubert Felle 《Planta》1988,176(2):248-255
In cells of Zea mays (root hairs, coleoptiles) and Riccia fluitans (rhizoids, thalli) intracellular Ca2+ and pH have been measured with double-barrelled microelectrodes. Free Ca2+ activities of 109–187 nM (Riccia rhizoids), 94–160 nM (Riccia thalli), 145–231 nM (Zea root hairs), 84–143 nM (Zea coleoptiles) were found, and therefore identified as cytoplasmic. In a few cases (Riccia rhizoids), free Ca2+ was in the lower millimolar range (2.3±0.8 mM). A change in external Ca2+ from 0.1 to 10 mM caused an initial and short transient increase in cytoplasmic free Ca2+ which finally levelled off at about 0.2 pCa unit below the control, whereas in the presence of cyanide the Ca2+ activity returned to the control level. It is suggested that this behaviour is indicative of active cellular Ca2+ regulation, and since it is energy-dependent, may involve a Ca2+-ATPase. Acidification of the cytoplasmic pH and alkalinization of the vacuolar pH lead to a simultaneous increase in cytoplasmic free Ca2+, while alkalinization of pHc decreased the Ca2+ activity. Since this is true for such remote organisms as Riccia and Zea, it may be concluded that regulation of cytoplasmic pH and free Ca2+ are interrelated. It is further concluded that double-barrelled microelectrodes are useful tools for investigations of intracellular ion activities in plant cells.Symbols and abbreviations m, m
membrane potential difference, changes thereof
- PVC
polyvinylchloride 相似文献