全文获取类型
收费全文 | 985篇 |
免费 | 6篇 |
国内免费 | 4篇 |
专业分类
995篇 |
出版年
2023年 | 6篇 |
2022年 | 14篇 |
2021年 | 9篇 |
2020年 | 2篇 |
2019年 | 79篇 |
2018年 | 65篇 |
2017年 | 45篇 |
2016年 | 4篇 |
2015年 | 4篇 |
2014年 | 73篇 |
2013年 | 66篇 |
2012年 | 40篇 |
2011年 | 25篇 |
2010年 | 9篇 |
2009年 | 10篇 |
2008年 | 12篇 |
2007年 | 13篇 |
2006年 | 2篇 |
2005年 | 6篇 |
2004年 | 9篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 17篇 |
1984年 | 73篇 |
1983年 | 68篇 |
1982年 | 61篇 |
1981年 | 49篇 |
1980年 | 37篇 |
1979年 | 37篇 |
1978年 | 22篇 |
1977年 | 39篇 |
1976年 | 22篇 |
1975年 | 20篇 |
1974年 | 12篇 |
1973年 | 12篇 |
排序方式: 共有995条查询结果,搜索用时 0 毫秒
51.
Akira Makino Anna Miyazaki Ayaka Tomoike Hiroyuki Kimura Kenji Arimitsu Masahiko Hirata Yoshiro Ohmomo Ryuichi Nishii Hidehiko Okazawa Yasushi Kiyono Masahiro Ono Hideo Saji 《Bioorganic & medicinal chemistry》2018,26(8):1609-1613
Tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR-TKIs) are used as molecular targeted therapy for non-small cell lung cancer (NSCLC) patients. The therapy is applied to the patients having EGFR-primary L858R mutation, but drug tolerance caused by EGFR-secondary mutation is occurred within one and half years. For the non-invasive detection of the EGFR-TKIs treatment positive patients by positron emission tomograpy (PET) imagaing, fluorine-18 labeled thienopyrimidine derivative, [18F]FTP2 was newly synthesized. EGFR inhibition assay, cell uptake study, and blocking study indicated [18F]FTP2 binds with high and selective affinity for EGFR with L858R mutation, and not with L858R/T790M dual mutations. On animal PET study using tumor bearing mice, H3255 cells expressing L858R mutated EGFR was more clearly visualized than H1975 cells expressing L858R/T790M dual mutated EGFR. [18F]FTP2 has potential for detecting NSCLC which is susceptible to EGFR-TKI treatment. 相似文献
52.
53.
An antibody preparation elicited against purified, lysosomal-solubilized NADH-cytochrome b5 reductase from rat liver microsomes was shown to interact with methemoglobin reductase of human erythrocytes by inhibiting the rate of erythrocyte cytochrome b5 reduction by NADH. The ferricyanide reductase activity of the enzyme was not inhibited by the antibody, suggesting that the inhibition of methemoglobin reductase activity may be due to interference with the binding of cytochrorme b5 to the flavoprotein. Under conditions of limiting concentrations of flavoprotein, the antibody inhibited the rate of methemoglobin reduction in a reconstituted system consisting of homogeneous methemoglobin reductase and cytochrome b5 from human erythrocytes. This inhibition was due to the decreased level of reduced cytochrome b5 during the steady state of methemoglobin reduction while the rate of methemoglobin reduction per reduced cytochrome b5 stayed constant, suggesting that the enzyme was not concerned with an electron transport between the reduced cytochrome b5 and methemoglobin.An antibody to purified, trypsin-solubilized cytochrome b5 from rat liver microsomes was shown to inhibit erythrocyte cytochrome b5 reduction by methemoglobin reductase and NADH to a lesser extent than microsomal cytochrome b5 preparations from rat liver (trypsin solubilized or detergent solubilized) and pig liver (trypsin solubilized). The results presented establish that soluble methemoglobin reductase and cytochrome b5 of human erythrocytes are immunochemically similar to NADH-cytochrome b5 reductase and cytochrome b5 of liver microsomes, respectively. 相似文献
54.
55.
56.
Joshua N. Farb 《Journal of molecular biology》2009,385(2):393-404
Cyanophycin, or poly-l-Asp-multi-l-Arg, is a non-ribosomally synthesized peptidic polymer that is used for nitrogen storage by cyanobacteria and other select eubacteria. Upon synthesis, it self-associates to form insoluble granules, the degradation of which is uniquely catalyzed by a carboxy-terminal-specific protease, cyanophycinase. We have determined the structure of cyanophycinase from the freshwater cyanobacterium Synechocystis sp. PCC6803 at 1.5-Å resolution, showing that the structure is dimeric, with individual protomers resembling aspartyl dipeptidase. Kinetic characterization of the enzyme demonstrates that the enzyme displays Michaelis-Menten kinetics with a kcat of 16.5 s− 1 and a kcat/KM of 7.5 × 10− 6 M− 1 s− 1. Site-directed mutagenesis experiments confirm that cyanophycinase is a serine protease and that Gln101, Asp172, Gln173, Arg178, Arg180 and Arg183, which form a conserved pocket adjacent to the catalytic Ser132, are functionally critical residues. Modeling indicates that cyanophycinase binds the β-Asp-Arg dipeptide residue immediately N-terminal to the scissile bond in an extended conformation in this pocket, primarily recognizing this penultimate β-Asp-Arg residue of the polymeric chain. Because binding and catalysis depend on substrate features unique to β-linked aspartyl peptides, cyanophycinase is able to act within the cytosol without non-specific cleavage events disrupting essential cellular processes. 相似文献
57.
Human apolipoprotein A-I (apo A-I) and its engineered constructs form discoidal lipid bilayers upon interaction with lipids in vitro. We now report the cloning, expression, and purification of apo A-I derived from zebrafish (Danio rerio), which combines with phospholipids to form similar discoidal bilayers and may prove to be superior to human apo A-I constructs for rapid reconstitution of seven-transmembrane helix receptors into nanoscale apolipoprotein bound bilayers (NABBs). We characterized NABBs by gel-filtration chromatography, native polyacrylamide gradient gel electrophoresis, UV-visible photobleaching difference spectroscopy, and fluorescence spectroscopy. We used electron microscopy to determine the stoichiometry and orientation of rhodopsin (rho)-containing NABBs prepared under various conditions and correlated stability and signaling efficiency of rho in NABBs with either one or two receptors. We discovered that the specific activity of G protein coupling for single rhos sequestered in individual NABBs was nearly identical with that of two rhos per NABB under conditions where stoichiometry and orientation could be inferred by electron microscopy imaging. Thermal stability of rho in NABBs was superior to that of rho in various commonly used detergents. We conclude that the NABB system using engineered zebrafish apo A-I is a native-like membrane mimetic system for G-protein-coupled receptors and discuss strategies for rapid incorporation of expressed membrane proteins into NABBs. 相似文献
58.
Lin Wu Arend van Peer Wenhua Song Hong Wang Mingjie Chen Qi Tan Chunyan Song Meiyan Zhang Dapeng Bao 《Gene》2013
During the life cycle of heterothallic tetrapolar Agaricomycetes such as Lentinula edodes (Berk.) Pegler, the mating type system, composed of unlinked A and B loci, plays a vital role in controlling sexual development and resulting formation of the fruit body. L. edodes is produced worldwide for consumption and medicinal purposes, and understanding its sexual development is therefore of great importance. A considerable amount of mating type factors has been indicated over the past decades but few genes have actually been identified, and no complete genetic structures of L. edodes B mating-type loci are available. In this study, we cloned the matB regions from two mating compatible L. edodes strains, 939P26 and 939P42. Four pheromone receptors were identified on each new matB region, together with three and four pheromone precursor genes in the respective strains. Gene polymorphism, phylogenetic analysis and distribution of pheromone receptors and pheromone precursors clearly indicate a bipartite matB locus, each sublocus containing a pheromone receptor and one or two pheromone precursors. Detailed sequence comparisons of genetic structures between the matB regions of strains 939P42, 939P26 and a previously reported strain SUP2 further supported this model and allowed identification of the B mating type subloci borders. Mating studies confirmed the control of B mating by the identified pheromone receptors and pheromones in L. edodes. 相似文献
59.
A A Suran 《Life sciences》1973,13(12):1779-1788
Causal relationships have been suggested between aspects of human behavior and hyperuricemia associated with low tissue activities of the x-linked enzyme hypoxanthine-guanine phosphoribosyl transferase. Brain is reported to have the highest content of HGPRT activity among body organs. Many studies have indicated that genetically distinct strains of mice exhibit strain-specific behavioral phenotypes. The present measurements of HGPRT were made to determine if genetically associated differences in regional distribution of brain HGPRT exist between several inbred mouse strains and if they were of sufficient magnitude to warrant a search for correlations with measures of behavior. Significant differences were found in overall brain content of HGPRT activity among seven inbred mouse strains, as well as in regional distribution of enzyme activity among eight structures of brains of each of the individual strains. 相似文献