全文获取类型
收费全文 | 1495篇 |
免费 | 70篇 |
出版年
2023年 | 5篇 |
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 8篇 |
2018年 | 27篇 |
2017年 | 11篇 |
2016年 | 20篇 |
2015年 | 32篇 |
2014年 | 48篇 |
2013年 | 107篇 |
2012年 | 82篇 |
2011年 | 87篇 |
2010年 | 61篇 |
2009年 | 46篇 |
2008年 | 61篇 |
2007年 | 113篇 |
2006年 | 79篇 |
2005年 | 84篇 |
2004年 | 106篇 |
2003年 | 92篇 |
2002年 | 104篇 |
2001年 | 21篇 |
2000年 | 18篇 |
1999年 | 14篇 |
1998年 | 18篇 |
1997年 | 32篇 |
1996年 | 15篇 |
1995年 | 11篇 |
1994年 | 17篇 |
1993年 | 18篇 |
1992年 | 18篇 |
1991年 | 16篇 |
1990年 | 14篇 |
1989年 | 9篇 |
1988年 | 7篇 |
1987年 | 13篇 |
1986年 | 10篇 |
1983年 | 8篇 |
1982年 | 12篇 |
1981年 | 20篇 |
1980年 | 20篇 |
1979年 | 8篇 |
1978年 | 5篇 |
1977年 | 10篇 |
1976年 | 6篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1970年 | 3篇 |
排序方式: 共有1565条查询结果,搜索用时 140 毫秒
81.
Synthesis and physical and physiological properties of 4'-thioRNA: application to post-modification of RNA aptamer toward NF-kappaB 下载免费PDF全文
We report herein full details of the preparation of 4′-thiouridine, -cytidine, -adenosine and -guanosine phosphoramidites based on our synthetic protocol via the Pummerer reaction. Fully modified 4′-thioRNAs containing four kinds of 4′-thioribonucleoside units were prepared according to the standard RNA synthesis. The Tm values and thermodynamic parameters of a series of duplexes were determined by UV melting and differential scanning calorimetry (DSC) measurements. The resulting overall order of thermal stabilities for the duplexes was 4′-thioRNA:4′-thioRNA >> 4′-thioRNA:RNA > RNA:RNA > RNA:DNA > 4′-thioRNA:DNA. In addition, it was shown that the dominant factor in the stability of the duplexes consisting of 4′-thioRNA was enthalpic in character. The CD spectra of not only 4′-thioRNA:RNA and 4′-thioRNA:4′-thioRNA but also 4′-thioRNA:DNA were all similar to those of duplexes in the A-conformation. The stability of 4′-thioRNA in human serum was 600 times greater than that of natural RNA. Neither the RNA:RNA nor the 4′-thioRNA:4′-thioRNA duplexes were digested under the same conditions. The first example of a post-modification of an RNA aptamer by 4′-thioribonucleoside units was demonstrated. Full modification of the aptamer thioRNA3 resulted in complete loss of binding activity. In contrast, modifications at positions other than the binding site were tolerated without loss of binding activity. The post-modified RNA aptamer thioRNA5 was thermally stabilized and resistant toward nuclease digestion. The results presented in this paper will, it is hoped, contribute to the development of 4′-thioRNA as a new generation of artificial RNA. 相似文献
82.
Miyazaki T Matsunaga T Miyazaki S Hokari S Komoda T 《Journal of cellular biochemistry》2004,93(3):503-512
We investigated time-course changes in the expression of receptor activator of nuclear factor-kappaB (RANK), its ligand (RANKL), osteoprotegerin (OPG), bone-type alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase (TRAP) in ovariectomized (OVX) rats. Samples of sera and coccyges were used for analysis of the enzyme activities and expression levels of proteins and mRNAs, and an immunohistochemical analysis was also performed. Serum BAP activity increased to 158.6% of the pre-operation value at 1 week after OVX, and then decreased to 38.7% at 8 weeks after OVX. On the other hand, the serum TRAP activity increased to 130.9% of the pre-operation level at 1 week after OVX, and was maintained at a high level, compared with the pre-operation level. The patterns of BAP and TRAP activity in the coccyges specimens were similar to those seen in the sera. The expression profiles of TRAP, RANK, and RANKL proteins in the coccyx specimens were similar to the pattern of serum TRAP activity, while the profiles of the BAP and OPG proteins were similar to the pattern of serum BAP activity in OVX rats. The changes in the mRNA expression levels of the osteogenic proteins were similar to those for protein expression. These biochemical changes in OVX rats were confirmed by immunohistochemical studies. Our results suggest that not only osteoclastogenesis accelerated but also osteoblastogenesis transiently increased during the early phase of osteoporosis. 相似文献
83.
Oxidative stress in the liver is sometimes accompanied by cholestasis. We investigated the localization and role of multidrug-resistance-associated protein (Mrp) 2, a biliary transporter involved in bile-salt-independent bile flow, under ethacrynic acid (EA)-induced acute oxidative stress. Normal Sprague-Dawley rat (SDR) and Mrp2-deficient Eisai hyperbilirubinemic rat (EHBR) livers were perfused with 500 microM EA. The release of glutamic pyruvic transaminase (GPT) and thiobarbituric-acid-reactive substances (TBARS) from EHBR liver was markedly delayed compared with that from SDR liver. This is mainly due to the higher basal level of glutathione (GSH) in EHBR liver (59.1 +/- 0.3 nmol/mg protein) compared with SDR liver (39.7 +/- 1.5 nmol/mg protein). EA similarly induced a rapid reduction in GSH followed by mitochondrial permeability transition in the isolated mitochondria from both SDR and EHBR. Internalization of Mrp2 was detected before nonspecific disruption of the canalicular membrane and GPT release in SDR liver perfused with 100 microM EA. SDR liver preperfused with hyperosmolar buffer (405 mosmol/L) for 30 min induced internalization of Mrp2 without changing the basal GSH level, while elimination of hepatic GSH by 300 microM EA perfusion was significantly delayed thereafter. Concomitantly, hepatotoxicity assessed by the release of GPT and TBARS was also significantly attenuated under hyperosmolar conditions. In conclusion, preserved cytosolic and intramitochondrial GSH is the key factor involved in the acute hepatotoxicity induced by EA and its susceptibility could be altered by the presence of Mrp2. 相似文献
84.
New chiral ferrocenyl ligands having chiral sulfinyl and phosphinyl groups were prepared. The palladium-catalyzed allylic substitution reaction using these chiral ligands showed good enantioselectivity. The mechanism for the asymmetric reaction is proposed on the basis of the stereochemical outcome. 相似文献
85.
Cytotoxicity and oxidative stress induced by the glyceraldehyde-related Maillard reaction products for HL-60 cells 总被引:1,自引:0,他引:1
Usui T Shizuuchi S Watanabe H Hayase F 《Bioscience, biotechnology, and biochemistry》2004,68(2):333-340
We demonstrated the cytotoxicity of glyceraldehyde-related Maillard reaction products for HL-60 cells. Glyceraldehyde-modified bovine serum albumin and glyceraldehyde-modified casein inhibited the proliferation of HL-60 cells. The reaction products formed from glyceraldehyde and Nalpha-acetyllysine had also a cytotoxic effect on HL-60 cells. The cytotoxic effect was prevented by N-acetylcysteine or pyrrolidinedithiocarbamate as the antioxidants. In addition, the reaction products depressed the intracellular glutathione level, and induced the reactive oxygen species (ROS) production. These results suggested that the glyceraldehyde-related advanced glycation end products (AGEs) induced the cytotoxicity and the oxidative stress.We previously reported that the glyceraldehyde-related AGE was identified as 1-(5-acetylamino-5-carboxypentyl)-3-hydroxy-5-hydroxymethyl-pyridinium, named GLAP (glyceraldehyde-derived pyridinium compound), formed from glyceraldehyde and Nalpha-acetyllysine (Biosci. Biotechnol. Biochem., 67, 930-932 (2003)). In this study, GLAP inhibited the proliferation of HL-60 cells, and the inhibitory effect was prevented by the antioxidants. Furthermore, GLAP depressed the intracellular glutathione level, and induced the ROS production.This work indicated the possibility that the cytotoxicity and the oxidative stress in the progression of diabetic complications and chronic renal disease might be induced by GLAP. 相似文献
86.
87.
Dof domain proteins: plant-specific transcription factors associated with diverse phenomena unique to plants 总被引:22,自引:0,他引:22
Yanagisawa S 《Plant & cell physiology》2004,45(4):386-391
88.
89.
Yano S 《Experimental & applied acarology》2004,32(4):243-248
Whether the spider mite Tetranychus urticae uses flying insects as vectors for phoretic dispersal was experimentally tested. Two bean plants were placed in a microcosm, and a mite population was introduced onto one of the plants. Either Phaenicia cuprina Wiedemann (Diptera: Calliphoridae) or Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) was then introduced into the microcosms as a hypothetical vector insect. T. urticae populations on the second bean plant were monitored to detect any evidence of phoretic dispersal. Instances of dispersal were detected at extremely low frequency, suggesting that phoretic dispersal of T. urticae mediated by winged insects is probably rare in the wild. 相似文献
90.
Toshima K Ozawa T Kimura T Matsumura S 《Bioorganic & medicinal chemistry letters》2004,14(11):2777-2779
The novel DNA interactive quinoxaline-carbohydrate hybrids possessing disaccharides as the carbohydrate moieties were designed and synthesized, and their DNA photocleaving abilities were evaluated in order to examine the effect of the disaccharide structures. The configurations of the glycosidic bonds in the disaccharide strongly affected the DNA photocleaving ability, and two beta-glycosidic bond linkages were very effective for the DNA photocleavage. Furthermore, the quinoxaline-disaccharide hybrids exhibited selective cytotoxicity against cancer cells with photoirradiation. 相似文献