全文获取类型
收费全文 | 5988篇 |
免费 | 398篇 |
国内免费 | 3篇 |
出版年
2021年 | 40篇 |
2020年 | 27篇 |
2019年 | 34篇 |
2018年 | 57篇 |
2017年 | 45篇 |
2016年 | 83篇 |
2015年 | 134篇 |
2014年 | 143篇 |
2013年 | 461篇 |
2012年 | 277篇 |
2011年 | 255篇 |
2010年 | 186篇 |
2009年 | 173篇 |
2008年 | 295篇 |
2007年 | 304篇 |
2006年 | 318篇 |
2005年 | 293篇 |
2004年 | 330篇 |
2003年 | 303篇 |
2002年 | 290篇 |
2001年 | 130篇 |
2000年 | 143篇 |
1999年 | 126篇 |
1998年 | 84篇 |
1997年 | 81篇 |
1996年 | 65篇 |
1995年 | 85篇 |
1994年 | 75篇 |
1993年 | 96篇 |
1992年 | 116篇 |
1991年 | 100篇 |
1990年 | 77篇 |
1989年 | 97篇 |
1988年 | 91篇 |
1987年 | 73篇 |
1986年 | 61篇 |
1985年 | 74篇 |
1984年 | 72篇 |
1983年 | 57篇 |
1982年 | 65篇 |
1981年 | 49篇 |
1980年 | 43篇 |
1979年 | 52篇 |
1978年 | 42篇 |
1977年 | 58篇 |
1976年 | 36篇 |
1975年 | 34篇 |
1974年 | 36篇 |
1973年 | 33篇 |
1969年 | 29篇 |
排序方式: 共有6389条查询结果,搜索用时 31 毫秒
991.
Kanji Takeo Reiko Tanaka Makoto Miyaji Kazuko Nishimura 《FEMS microbiology letters》1995,129(2-3):231-235
Abstract Stationary-phase cells of Cryptococcus neoformans displayed two morphological characteristics: virtually all the cells were unbudded even in the early stationary phase and even when grown in rich media, and average cell size increased from that of exponential-phase cells. DNA contents for small and large stationary-phase cells were determined by quantitative fluorescence microscopy after DNA staining with propidium iodide or DAPI. Small cells contained G, DNA, whereas large unbudded cells had either a G2 or G1 DNA content, indicating that Cr. neoformans can enter into the stationary phase from either the G1 or G2 period. 相似文献
992.
Summary We describe a genetic polymorphism of a human cellular polypeptide with mol. wt. 100,000, detected in peripheral blood lymphocytes by high resolution two-dimensional electrophoresis. Three different electrophoretic types (1-1, 2-1, and 2-2) of the polypeptide have been identified. Family and population studies indicate that the three phenotypes of the polypeptide are determined by two common alleles at a single autosomal locus. The polypeptide occurs in the cytosol and is one of the abundant polypeptides of B-lymphoblastoid cells, T-lymphoblastoid cells, fibroblasts, and HeLa cells. The data indicate that the cytosol polypeptide with mol.wt. 100,000 shows a genetic polymorphism determined by aew autosomal locus. It is proposed that the polypeptide and its locus be temporarily designated cytosol 100k polypeptide (C100k polypeptide) and C100P, respectively. In a Japanese population, the gene frequencies of C100P
1 and C100P
2 were 0.907 and 0.093, respectively. 相似文献
993.
994.
Hideo Kurebayashi Akira Tanaka Tsutomu Yamaha 《Archives of biochemistry and biophysics》1982,215(2):433-443
The mechanism of microsomal oxidative deamination of alicyclic primary amines: cyclopentylamine, cyclohexylamine, cycloheptylamine, 1- and 2-aminoindan, 1- and 2-aminotetralin, was studied under an atmosphere of 18O2 or in a medium containing H218O. The oxygen-18 contents of the products determined by gas-liquid chromatography/mass spectrometry revealed that almost all (75–100 atom%) of the oxygen of oximes was derived from molecular oxygen, whereas a part (4–25 atom% ) of the oxygen of ketones. The studies on the hydrolysis of oximes and the oxygen exchange reaction of ketones proved that the latter proceeded at a considerable rate () and the former made a minor contribution, to explain why the major portion (75–96 atom%) of the oxygen in ketones was derived from water. The results support the mechanism that microsomal deamination proceeds mainly through a carbinolamine intermediate, which is initially hydroxylated at the α carbon to the amino group, partially equilibrating with the imine, and then rearranges to form a ketone and ammonia. 相似文献
995.
Ayumu Niida Yoko Kanematsu-Yamaki Tomoko Asakawa Yoshimasa Ishimura Hisashi Fujita Kouta Matsumiya Naoki Nishizawa Yusuke Adachi Taisuke Mochida Kazue Tsuchimori Mariko Yoneyama-Hirozane Junichi Sakamoto Hideki Hirabayashi Hideo Fukui Shiro Takekawa Taiji Asami 《Bioorganic & medicinal chemistry》2018,26(3):566-572
Neuropeptide Y2 receptor (Y2R) agonism is an important anorectic signal and a target of antiobesity drug discovery. Recently, we synthesized a short-length Y2R agonist, PYY-1119 (4-imidazolecarbonyl-[d-Hyp24,Iva25,Pya(4)26,Cha27,36,γMeLeu28,Lys30,Aib31]PYY(23–36), 1) as an antiobesity drug candidate. Compound 1 induced marked body weight loss in diet-induced obese (DIO) mice; however, 1 also induced severe vomiting in dogs at a lower dose than the minimum effective dose administered to DIO mice. The rapid absorption of 1 after subcutaneous administration caused the severe vomiting. Polyethylene glycol (PEG)- and alkyl-modified derivatives of 1 were synthesized to develop Y2R agonists with improved pharmacokinetic profiles, i.e., lower maximum plasma concentration (Cmax) and longer time at maximum concentration (Tmax). Compounds 5 and 10, modified with 20?kDa PEG at the N-terminus and eicosanedioic acid at the Lys30 side chain of 1, respectively, showed high Y2R binding affinity and induced significant body weight reduction upon once-daily administration to DIO mice. Compounds 5 and 10, with their relatively low Cmax and long Tmax, partially attenuated emesis in dogs compared with 1. These results indicate that optimization of pharmacokinetic properties of Y2R agonists is an effective strategy to alleviate emesis induced by Y2R agonism. 相似文献
996.
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
997.
Hideo Satsu Sohei Awara Tomonori Unno Makoto Shimizu 《Bioscience, biotechnology, and biochemistry》2018,82(4):636-646
AbstractInhibition of excessive fructose intake in the small intestine could alleviate fructose-induced diseases such as hypertension and non-alcoholic fatty liver disease. We examined the effect of phytochemicals on fructose uptake using human intestinal epithelial-like Caco-2 cells which express the fructose transporter, GLUT5. Among 35 phytochemicals tested, five, including nobiletin and epicatechin gallate (ECg), markedly inhibited fructose uptake. Nobiletin and ECg also inhibited the uptake of glucose but not of L-leucine or Gly-Sar, suggesting an inhibitory effect specific to monosaccharide transporters. Kinetic analysis further suggested that this reduction in fructose uptake was associated with a decrease in the apparent number of cell-surface GLUT5 molecules, and not with a change in the affinity of GLUT5 for fructose. Lastly, nobiletin and ECg suppressed the permeation of fructose across Caco-2 cell monolayers. These findings suggest that nobiletin and ECg are good candidates for preventing diseases caused by excessive fructose intake. 相似文献
998.
Kazunori Nishimura Sumiko Watanabe Tsunehisa Kaku Setsuo Sugishima 《Bioscience, biotechnology, and biochemistry》2018,82(5):821-826
Serum starvation induces binucleation in HeLa cells, but the effects of serum starvation on mitosis and the significance of binucleation remain unknown. We investigated the effect of serum starvation on mitosis and analyzed the growth of binucleated cells. The frequency of binucleation caused by cytokinesis failure in DMEM without FBS (0% medium) was higher than that in DMEM with FBS (10% medium). In 0% medium, the metaphase spindle location was off-center, and RhoA localization significantly lacked symmetry. The frequency of the extension of intercellular bridge with the midbody in 0% medium was significantly higher than that in 10% medium. Moreover, all mononucleated mitotic cells caused bipolar mitosis and produced only mononucleated daughter cells, but binucleated cells produced various nucleated cells by multipolar mitosis in 0% medium. These results suggest that serum starvation may have various effects on mitosis, and binucleated cells may be related to formation of aneuploidy. 相似文献
999.
Identification of 2-phenylethanol with a rose-like odor from anal sac secretions of the small Indian mongoose (Herpestes auropunctatus) 总被引:1,自引:0,他引:1
Tamako Miyazaki Katsushi Nakata Takashi Nishimura Shintaro Abe Tetsuro Yamashita 《Bioscience, biotechnology, and biochemistry》2018,82(2):232-237
The small Indian mongoose (Herpestes auropunctatus) is an invasive species in Okinawa and Amami-Oshima, Japan. Major strategies for their eradication have been the use of baited traps, which suffer from decreasing efficiency with declining populations and the bycatch of native animals. To address these concerns, mongoose-specific lures are required. In this study, we aimed to identify species- and/or sex-specific compounds from anal sac secretions of small Indian mongooses. Volatile compounds emitted from male and female mongoose anal sac secretions were analyzed by thermal desorption-gas chromatography-mass spectrometry. In addition to several fatty acids, 2-phenylethanol was identified as a minor compound, which is uncommon in mammalian secretions but a dominant odorant in roses. Female samples emitted higher levels of 2-phenylethanol than male samples did. These findings indicate that 2-phenylethanol is a female-specific volatile compound of anal sac secretions in small Indian mongooses, and it may be useful as an ingredient of mongoose-specific scent lures. 相似文献
1000.
Hiroyuki Kimura Saki Yamauchi Hidekazu Kawashima Kenji Arimitsu Yusuke Yagi Yuji Nakamoto Kaori Togashi Masahiro Ono Hideo Saji 《Bioorganic & medicinal chemistry letters》2018,28(17):2949-2952
The tripeptide formyl–Met–Leu–Phe (fMLF) is a prototype of N-formylated chemotactic peptides for neutrophils owing to its ability to bind and activate the G protein-coupled formyl peptide receptor (FPR). Here, we developed an 18F-labeled fMLF derivative targeting FPR as a positron emission tomography (PET) imaging probe for bacterial infections. The study demonstrates that the fMLF derivative fMLFXYk(FB)k (X?=?Nle) has a high affinity for FPR (Ki?=?0.62?±?0.13?nM). The radiochemical yield and purity of [18F]fMLFXYk(FB)k were 16% and >96%, respectively. The in vivo biodistribution study showed that [18F]fMLFXYk(FB)k uptake was higher in the bacterial infected region than in the non-infected region. We observed considerably higher infection-to-muscle ratio of 4.6 at 60?min after [18F]fMLFXYk(FB)k injection. Furthermore, small-animal PET imaging studies suggested that [18F]fMLFXYk(FB)k uptake in the bacterial infected region was clearly visualized 60?min after injection. 相似文献