全文获取类型
收费全文 | 2147篇 |
免费 | 129篇 |
国内免费 | 3篇 |
专业分类
2279篇 |
出版年
2023年 | 6篇 |
2022年 | 13篇 |
2021年 | 20篇 |
2020年 | 11篇 |
2019年 | 22篇 |
2018年 | 24篇 |
2017年 | 25篇 |
2016年 | 27篇 |
2015年 | 65篇 |
2014年 | 80篇 |
2013年 | 155篇 |
2012年 | 134篇 |
2011年 | 127篇 |
2010年 | 77篇 |
2009年 | 83篇 |
2008年 | 148篇 |
2007年 | 137篇 |
2006年 | 112篇 |
2005年 | 136篇 |
2004年 | 129篇 |
2003年 | 156篇 |
2002年 | 176篇 |
2001年 | 24篇 |
2000年 | 21篇 |
1999年 | 24篇 |
1998年 | 42篇 |
1997年 | 27篇 |
1996年 | 15篇 |
1995年 | 24篇 |
1994年 | 21篇 |
1993年 | 21篇 |
1992年 | 24篇 |
1991年 | 14篇 |
1990年 | 19篇 |
1989年 | 14篇 |
1988年 | 11篇 |
1987年 | 12篇 |
1986年 | 8篇 |
1985年 | 10篇 |
1984年 | 13篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1980年 | 10篇 |
1977年 | 6篇 |
1976年 | 5篇 |
1975年 | 6篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1968年 | 4篇 |
排序方式: 共有2279条查询结果,搜索用时 15 毫秒
81.
Two stereoisomers of a castasterone/ponasterone A hybrid compound, the (20R,22R) and (20R,22S)-isomers of 2alpha,3alpha,20,22-tetrahydroxy-5alpha-cholestan-6-one, were synthesized stereoselectively and their binding activity to the ecdysteroid receptor was determined. From the concentration-response curve for the inhibition of the incorporation of tritiated ponasterone A into ecdysteroid receptor containing insect cells, the concentration (IC50) required to inhibit 50% of the incorporation of radioactivity into cells was evaluated. The IC50 values of the (22R)- and (22S)-isomers were determined to be 0.30 and 38.9 microM against Kc cells, respectively, indicating that the (22R)-isomer is about 100 times more potent than the corresponding (22S)-isomer. IC50 values of these compounds against lepidopteran Sf-9 cells were determined to be 0.36 and 12.9 microM, respectively. The molting hormonal effect was examined in a Chilo suppressalis integument system and the 50% effective concentration for the stimulation of N-acetylglucosamine incorporation into the cultured integument was determined to be 2.7 microM for the (22R)-isomer, while the (22S)-isomer was inactive. On the other hand, both isomers did not show brassinolide-like activity in the rice lamina inclination assay. 相似文献
82.
Flower color modulations of Torenia hybrida by downregulation of chalcone synthase genes with RNA interference 总被引:1,自引:0,他引:1
Fukusaki E Kawasaki K Kajiyama S An CI Suzuki K Tanaka Y Kobayashi A 《Journal of biotechnology》2004,111(3):229-240
Suppression of biosynthetic genes involved in flower color formation is an important approach for obtaining target flower colors. Here we report that flower color of the garden plant Torenia hybrida was successfully modulated by RNA interference (RNAi) against a gene of chalcone synthase (CHS), a key enzyme for anthocyanin and flavonoid biosynthesis. By using each of the coding region and the 3'-untranslated region of the CHS mRNA as an RNAi target, exhaustive and gene-specific gene silencing were successfully induced, and the original blue flower color was modulated to white and pale colors, respectively. Our results indicate that RNAi is quite useful for modulations of flower colors of commercially important garden plants. 相似文献
83.
Iyama T Ebara H Tarusawa Y Uebayashi S Sekijima M Nojima T Miyakoshi J 《Bioelectromagnetics》2004,25(8):599-606
A beam formed radiofrequency (RF) exposure-incubator employing a horn antenna, a dielectric lens, and a culture case in an anechoic chamber is developed for large scale in vitro studies. The combination of an open type RF exposure source and a culture case through which RF is transmitted realizes a uniform electric field (+/-1.5 dB) in a 300 x 300 mm area that accommodates 49 35 mm diameter culture dishes. This large culture dish area enables simultaneous RF exposure of a large number of cells or various cell lines. The RF exposure source operates at 2142.5 MHz corresponding to the middle frequency of the downlink band of the International Mobile Telecommunication 2000 (IMT-2000) cellular system. The dielectric lens, which has a gain of 7 dB, focuses RF energy in the direction of the culture case and provides a uniform electric field. The culture case is sealed and connected to the main unit for environmental control, located outside the anechoic chamber, via ducts. The temperature at the center of the tray, which contains the culture dishes in the culture room, is maintained at 37.0 +/- 0.2 degrees C by air circulation. In addition, the appropriate CO2 density and humidity supplied to the culture case realizes stable long-term culture conditions. Specific absorption rate (SAR) dosimetry is performed using an electric field measurement technique and the Finite Difference Time Domain (FDTD) calculation method. The results indicate that the mean SAR of the culture fluid at the bottom of the 49 (7 x 7 array) culture dishes used in the in vitro experiments is 0.175 W/kg for an antenna input power of 1 W and the standard deviation of the SAR distribution is 59%. When only 25 culture dishes (5 x 5 array) are evaluated, the mean SAR is 0.139 W/kg for the same antenna input power and the standard deviation of the SAR distribution is 47%. The proliferation of the H4 cell line in 72 h in a pair of RF exposure-incubators reveals that the culture conditions are equivalent to those of a common CO2 incubator. 相似文献
84.
The development of synthetic biodegradable polymers, such as poly(alpha-hydroxy acid), is particularly important for constructing medical devices, including scaffolds and sutures, and has attracted growing interest in the biomedical field. Here, we report a novel approach to preparing high molecular weight poly(malic acid) (HMW--PMA) as a biodegradable and bioabsorbable water-soluble polymer. We investigated in detail the reaction conditions for the simple direct polycondensation of l-malic acid, including the reaction times, temperatures, and catalysts. The molecular weight of synthesized alpha,beta-PMA is dependent on both the reaction temperature and time. The optimum reaction condition to obtain alpha,beta-PMA by direct polycondensation using tin(II) chloride as a catalyst was thus determined to be 110 degrees C for 45 h with a molecular weight of 5300. The method for alpha,beta-PMA synthesis established here will facilitate production of alpha,beta-PMA of various molecular weights, which may have a potential utility as biomaterials. 相似文献
85.
Furuyama F Murakami M Tanaka E Hida H Miyazawa D Oiwa T Isobe Y Nishino H 《American journal of physiology. Regulatory, integrative and comparative physiology》2003,285(6):R1439-R1445
Compared with other rat strains, the inbred FOK rat is extremely heat tolerant. This increased heat tolerance is due largely to the animal's enhanced saliva spreading abilities. The aims of the present study were to 1) quantify the heat tolerance capacity of FOK rats and 2) determine the regulatory mode of the enhanced salivary cooling in these animals. Various strains of rats were acutely exposed to heat. In the heat-intolerant strains, saliva spreading was insufficient and the core temperature (Tc) rose rapidly. In contrast, FOK rats maintained an elevated Tc plateau (39.5 +/- 0.7 degrees C) for 5-6 h over a wide range of ambient temperatures (Ta) (37.5-42.5 degrees C). In hot environments the FOK rats secreted copious amounts of saliva and spread it over more than the entire ventral body surface. FOK rats had a low Tc threshold for salivation, and the salivation rate increased linearly in proportion to the Tc deviation from the threshold. No strain difference or temperature effect was observed in the saliva secretion rate from in vitro submandibular glands perfused by sufficient doses of ACh. These results suggest that 1) the ability of FOK rats to maintain a moderate steady-state hyperthermia (39.5 +/- 0.7 degrees C) over a wide Ta range is enabled by a lowered threshold Tc for salivation and functional negative-feedback control of saliva secretion and 2) strain differences in ability to endure heat stress are mainly attributable to changes in the thermoregulatory control system rather than altered secretory abilities of the salivary glands. 相似文献
86.
Kurimoto A Ogino T Ichii S Isobe Y Tobe M Ogita H Takaku H Sajiki H Hirota K Kawakami H 《Bioorganic & medicinal chemistry》2003,11(24):5501-5508
Recently, we have reported the 8-hydroxyadenine derivatives (2–4) as a novel class of interferon (IFN) inducing agents. In the present study, a series of 8-hydroxyadenines, which possess various amino moieties at the adenine C(2)-position, were synthesized and evaluated for their ability to induce endogenous IFN in comparison to the known active agent, Imiquimod. Among the compounds prepared, compound 9o possessing a 2-methoxyethylamino group at C(2)-position of adenine was found to exhibit potent IFN inducing activity in vivo. Compound 9o induced IFN from the dosage of 0.1 mg/kg, which was 30-fold potent than that of Imiquimod, and showed a good oral bioavailability (F=81%). 相似文献
87.
88.
Tobe M Isobe Y Tomizawa H Nagasaki T Obara F Hayashi H 《Bioorganic & medicinal chemistry》2003,11(4):609-616
We synthesized various 6-fluoro-7-(1-piperazino)quinazolines based on the structure of 1 and evaluated their inhibitory activities toward both TNF-alpha production and T cell proliferation responses. Among these compounds, 7a, having the 3,4-(methylenedioxy)phenyl moiety at the C(4)-position of the quinazoline ring, showed both inhibitory activities. Furthermore, the oral treatment with 7a exhibited an anti-inflammatory effect in rats with adjuvant arthritis as well as an inhibitory activity toward LPS-induced TNF-alpha production. 相似文献
89.
Vigouroux S Furukawa Y Farout L J Kish S Briand M Briand Y 《Journal of neurochemistry》2003,84(2):392-396
Many neurodegenerative diseases are characterized by ubiquitin-positive protein aggregates or inclusion bodies. Ubiquitin-conjugated proteins are degraded by the 20/26S proteasome, and reduced proteasome peptidase activities in brain homogenates have been reported in pathologic lesions of Parkinson's and Alzheimer's diseases. However, it is unknown whether crude extracts of human brain contain other proteases having peptidase activities. We found a novel protease of molecular weight of approximately 105 kDa in normal human brain, which exhibited trypsin-like (T-L) and chymotrypsin-like (ChT-L) activities (corresponding to 52% and 21% of the total activities in crude extracts) but not peptidyl glutamyl peptide hydrolase activity. Both T-L and ChT-L activities of this protease were partially inhibited by proteasome inhibitors (MG132, lactacystin) and, in contrast to those of the proteasome, also by sodium dodecyl sulfate. A simple method to obtain a brain fraction specific to the 20/26S proteasome was developed. Our human brain data suggest that T-L and ChT-L activity levels of the proteasome reported previously may include those of the 105 kDa protease, an enzyme of as yet unknown biological significance, and that it is necessary to separate the proteasome from this protease to evaluate the actual status of the ubiquitin-proteasome system in neurodegenerative disorders. 相似文献
90.
Factors controlling the uptake of yeast copper/zinc superoxide dismutase into mitochondria 总被引:9,自引:0,他引:9
Field LS Furukawa Y O'Halloran TV Culotta VC 《The Journal of biological chemistry》2003,278(30):28052-28059
We have previously shown that a fraction of yeast copper/zinc-superoxide dismutase (SOD1) and its copper chaperone CCS localize to the intermembrane space of mitochondria. In the present study, we have focused on the mechanism by which SOD1 is partitioned between cytosolic and mitochondrial pools. Using in vitro mitochondrial import assays, we show that only a very immature form of the SOD1 polypeptide that is apo for both copper and zinc can efficiently enter the mitochondria. Moreover, a conserved disulfide in SOD1 that is essential for activity must be reduced to facilitate mitochondrial uptake of SOD1. Once inside the mitochondria, SOD1 is converted to an active holo enzyme through the same post-translational modifications seen with cytosolic SOD1. The presence of high levels of CCS in the mitochondrial intermembrane space results in enhanced mitochondrial accumulation of SOD1, and this apparently involves CCS-mediated retention of SOD1 within mitochondria. This retention of SOD1 is not dependent on copper loading of the enzyme but does require protein-protein interactions at the heterodimerization interface of SOD1 and CCS as well as conserved cysteine residues in both molecules. A model for how CCS-mediated post-translational modification of SOD1 controls its partitioning between the mitochondria and cytosol will be presented. 相似文献