全文获取类型
收费全文 | 3167篇 |
免费 | 182篇 |
国内免费 | 4篇 |
出版年
2023年 | 9篇 |
2022年 | 10篇 |
2021年 | 39篇 |
2020年 | 37篇 |
2019年 | 34篇 |
2018年 | 70篇 |
2017年 | 65篇 |
2016年 | 94篇 |
2015年 | 142篇 |
2014年 | 153篇 |
2013年 | 197篇 |
2012年 | 224篇 |
2011年 | 220篇 |
2010年 | 150篇 |
2009年 | 129篇 |
2008年 | 203篇 |
2007年 | 224篇 |
2006年 | 180篇 |
2005年 | 181篇 |
2004年 | 196篇 |
2003年 | 186篇 |
2002年 | 171篇 |
2001年 | 33篇 |
2000年 | 22篇 |
1999年 | 24篇 |
1998年 | 34篇 |
1997年 | 26篇 |
1996年 | 22篇 |
1995年 | 11篇 |
1994年 | 14篇 |
1993年 | 15篇 |
1992年 | 18篇 |
1991年 | 8篇 |
1990年 | 14篇 |
1989年 | 12篇 |
1988年 | 14篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 18篇 |
1984年 | 12篇 |
1983年 | 9篇 |
1982年 | 15篇 |
1981年 | 11篇 |
1980年 | 8篇 |
1979年 | 9篇 |
1977年 | 17篇 |
1973年 | 8篇 |
1971年 | 6篇 |
1970年 | 8篇 |
1967年 | 5篇 |
排序方式: 共有3353条查询结果,搜索用时 15 毫秒
991.
Katzenellenbogen E Kocharova NA Zatonsky GV Shashkov AS Korzeniowska-Kowal A Gamian A Bogulska M Knirel YA 《Carbohydrate research》2005,340(2):263-270
The O-polysaccharide of Hafnia alvei PCM 1189 consists of D-glucose, D-galactose, D-GalNAc and D-GlcA and lacks the strict regularity. The intact and carboxyl-reduced polysaccharides as well as oligosaccharides obtained by partial acid hydrolysis were studied by chemical and enzymatic analyses, methylation and NMR spectroscopy. The following structure was established for the O-polysaccharide, which is built up of branched hexa- to octasaccharide repeating units differing in the number of lateral glucose residues: [structure: see text] where the glucose residues shown in italics are nonstoichiometric substituents. The repeating units include also a minor O-acetyl group, whose position was not determined. 相似文献
992.
The effect of bacitracin on the activity of proteases extracted from pollen and sprouts of various plant species and compared to five commercially available proteases was studied. Bacitracin stimulates some pollen proteolytic enzyme activities, contrary to its inhibitory influence on proteases from the other sources. Proteases from maize pollen, inhibited by pepstatin and phenylmethylsulfonyl fluoride, immediately accelerate their activities after addition of bacitracin to the reaction mixture. The stimulating influence of peptide antibiotic on pollen proteases of some plants is unexpected and molecular mechanism of this phenomenon requires a further elucidation. The augmentation of allergenic response caused by pollen enzymes and drugs containing bacitracin is discussed. 相似文献
993.
Bugreev DV Golub EI Stasiak AZ Stasiak A Mazin AV 《The Journal of biological chemistry》2005,280(29):26886-26895
Rad51 and its meiotic homolog Dmc1 are key proteins of homologous recombination in eukaryotes. These proteins form nucleoprotein complexes on single-stranded DNA that promote a search for homology and that perform DNA strand exchange, the two essential steps of genetic recombination. Previously, we demonstrated that Ca2+ greatly stimulates the DNA strand exchange activity of human (h) Rad51 protein (Bugreev, D. V., and Mazin, A. V. (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 9988-9993). Here, we show that the DNA strand exchange activity of hDmc1 protein is also stimulated by Ca2+. However, the mechanism of stimulation of hDmc1 protein appears to be different from that of hRad51 protein. In the case of hRad51 protein, Ca2+ acts primarily by inhibiting its ATPase activity, thereby preventing self-conversion into an inactive ADP-bound complex. In contrast, we demonstrate that hDmc1 protein does not self-convert into a stable ADP-bound complex. The results indicate that activation of hDmc1 is mediated through conformational changes induced by free Ca2+ ion binding to a protein site that is distinct from the Mg2+.ATP-binding center. These conformational changes are manifested by formation of more stable filamentous hDmc1.single-stranded DNA complexes. Our results demonstrate a universal role of Ca2+ in stimulation of mammalian DNA strand exchange proteins and reveal diversity in the mechanisms of this stimulation. 相似文献
994.
Deng Z Coudray C Gouzoux L Mazur A Rayssiguier Y Pépin D 《Biological trace element research》2000,76(3):245-256
Aluminum (Al) is toxic to certain biological systems and has been implicated as a neurotoxic agent in the pathogenesis of
Alzheimer’s disease. Intestinal absorption of Al is very low (0.1%), but many organic dietary components are potential chelators
of Al and may enhance its absorption and tissue distribution. We examined the effects of acute and chronic coingestion of
AlCl3 with different polyphenolic acids on Al retention and compared to citrate in rats. In experiment 1, animals fasted for 14
h were dosed orally with demineralized water, Al chloride, Al chloride plus sodium citrate, or Al chloride plus a polyphenol
acid. Blood samples were taken before and 2 h after the gavage and animals were killed 6 h later. In experiment 2, the rats
were adapted on a purified diet for 1 wk and received the following for 4 wk in their experimental diets: AlCl3, except group 1, plus citrate or a polyphenol acid, except groups 1 and 2. Animals were killed and blood and tissues were
sampled. In experiment 1, citrate highly enhanced Al absorption and its tissue retention. Gallic and chlorogenic acids significantly
increased tibia and kidney Al levels compared to the Al group. In experiment 2, Al levels in the urine were significantly
increased in all the Al groups compared to the control group. Significantly higher Al levels in the tibia, kidney, and brain
were observed in the citrate group and a significant increase in brain Al level was also noted in the chlorogenic acid group
compared to AlCl3 group. This may suggest a possible relation structure-activity of polyphenol acids. However, further studies are necessary
to better understand the influence of polyphenol acids on Al metabolism, in particular that of chlorogenic acid. 相似文献
995.
Gesing A Modrzejewska H Karbownik M Sewerynek E Greger J Lewinski A 《Neuro endocrinology letters》2000,21(6):453-459
OBJECTIVES: Thymidine kinase (TK, EC 2.7.1.21) is a part of the pyrimidine salvage pathway, involved in DNA synthesis. In turn, adenosine kinase (AK, EC 2.7.1.20) functions as a part of the purine metabolic pathway, involved in DNA synthesis. Melatonin (Mel) is an indoleamine which is known to inhibit growth processes in the thyroid gland and also in other endocrine and non-endocrine tissues. The aim of our study was to examine TK and AK activities in homogenates of the rat thyroid lobes remaining after contralateral hemithyroidectomy (hemiTx); additionally, incubations with Mel (10(-6), 10(-9), and 10(-12) M) were performed. METHODS: The experiment was performed on young male Wistar rats (6-week old). The enzyme activities were measured by ascending chromatography and expressed as the amounts of radioactive reaction products of the phosphorylation of dThd (for TK) and of dAdo (for AK). RESULTS: 1. HemiTx increased TK activity in homogenates of the remaining thyroid lobe; 2. Mel increased TK activity in all the groups (intact, sham-operated- and hemiTx-rats), except for the concentrations of 10(-9) and 10(-12) M in the hemiTx-rats, in which the increasing effects of Mel on TK activity reached the borderline statistical significance only; 3. Mel increased the AK activity in intact and in shamTx animals; 4. No statistically significant changes were found in AK activity following Mel in vitro in the incubated remaining thyroid lobes, collected from hemiTx-rats. 相似文献
996.
We report on the ultrastructural distribution of arginine-vasopressin (AVP) in the heart of newborn rats using pre-embedding peroxidase-antiperoxidase immunocytochemistry with a polyclonal AVP antibody for electron microscopy. Positive labelling for AVP was localized in endothelial cells of main coronary arteries and cardiac vessels of smaller diameter (microvessels). Examination of the right coronary artery showed that approximately 58% of the endothelial cells were positive for AVP. Immunoreactivity to AVP in the cytoplasm of arterial endothelium predominated in association with the membranes of granular endoplasmic reticulum and in subplasmalemmal areas. The endothelium of small vessels exhibits less endoplasmic reticulum, but still shows AVP immunoprecipitate in the cytoplasm. It is suggested that endothelial AVP may contribute to vasomotor control of the coronary circulation in the early stages of postnatal development. AVP antibody also labelled some fibroblast/fibroblast-like cells associated with the coronary arteries and microvessels; thus, these cells as well as the endothelium appear to be a source of AVP in the newborn rat heart. The functional significance of these findings is discussed. 相似文献
997.
Ashraf SS Guenther RH Ansari G Malkiewicz A Sochacka E Agris PF 《Cell biochemistry and biophysics》2000,33(3):241-252
Naturally occurring nucleoside modifications are an intrinsic feature of transfer RNA (tRNA), and have been implicated in the efficiency, as well as accuracy-of codon recognition. The structural and functional contributions of the modified nucleosides in the yeast tRNA(Phe) anticodon domain were examined. Modified nucleosides were site-selectively incorporated, individually and in combinations, into the heptadecamer anticodon stem and loop domain, (ASL(Phe)). The stem modification, 5-methylcytidine, improved RNA thermal stability, but had a deleterious effect on ribosomal binding. In contrast, the loop modification, 1-methylguanosine, enhanced ribosome binding, but dramatically decreased thermal stability. With multiple modifications present, the global ASL stability was mostly the result of the individual contributions to the stem plus that to the loop. The effect of modification on ribosomal binding was not predictable from thermodynamic contributions or location in the stem or loop. With 4/5 modifications in the ASL, ribosomal binding was comparable to that of the unmodified ASL. Therefore, modifications of the yeast tRNA(Phe) anticodon domain may have more to do with accuracy of codon reading than with affinity of this tRNA for the ribosomal P-site. In addition, we have used the approach of site-selective incorporation of specific nucleoside modifications to identify 2'O-methylation of guanosine at wobble position 34 (Gm34) as being responsible for the characteristically enhanced chemical reactivity of C1400 in Escherichia coli 16S rRNA upon ribosomal footprinting of yeast tRNA(Phe). Thus, effective ribosome binding of tRNA(Phe) is a combination of anticodon stem stability and the correct architecture and dynamics of the anticodon loop. Correct tRNA binding to the ribosomal P-site probably includes interaction of Gm34 with 16S rRNA C1400. 相似文献
998.
Kłapcińska B Poprzecki S Danch A Sobczak A Kempa K 《Biological trace element research》2005,108(1-3):1-15
The selenium status and the relationship of whole-blood selenium and plasma homocysteine are reported for healthy human subjects
living in Upper Silesia. A total of 1063 individuals (627 male and 436 female) examined for whole-blood selenium were subdivided
into six groups according to age; the youngest included adolescents (n=143) aged 10–15 yr, and the oldest were centenarians (n=132). The mean Se content was relatively low (62.5±18.4 μg/L), and it tended to be higher in men (65.9±17.2 μg/L) than in
women (57.5±18.9 μg/L). Selenium levels appeared to be age dependent, as the highest values were observed in young and middle-age
adults (21–40 yr), whereas they were significantly lower in adolescents and in the elderly. In more than 40% of apparently
healthy adults (aged 21–69 yr), the Se concentration was within the range 60–80 μg/L (i.e., below the lower limit of the nutritional
adequacy range [80 μg/L]). A significant inverse correlation between whole-blood selenium and plasma total homocysteine was
detected in a smaller population sample of middle-aged and elderly persons (n=204). 相似文献
999.
Thermolytic CpG-containing DNA oligonucleotides as potential immunotherapeutic prodrugs 总被引:3,自引:2,他引:1
Grajkowski A Pedras-Vasconcelos J Wang V Ausín C Hess S Verthelyi D Beaucage SL 《Nucleic acids research》2005,33(11):3550-3560
A CpG-containing DNA oligonucleotide functionalized with the 2-(N-formyl-N-methyl)aminoethyl thiophosphate protecting group (CpG ODN fma1555) was prepared from phosphoramidites 1a–d using solid-phase techniques. The oligonucleotide behaved as a prodrug by virtue of its conversion to the well-studied immunomodulatory CpG ODN 1555 through thermolytic cleavage of the 2-(N-formyl-N-methyl)aminoethyl thiophosphate protecting group. Such a conversion occurred at 37°C with a half-time of 73 h. The immunostimulatory properties of CpG ODN fma1555 were evaluated in two in vivo assays, one of which consisted of mice challenged in the ear with live Leishmania major metacyclic promastigotes. Local intradermal administration of CpG ODN fma1555 was as effective as that of CpG ODN 1555 in reducing the size of Leishmania lesions over time. In a different infectious model, CpG ODN 1555 prevented the death of Tacaribe-infected mice (43% survival) when administered between day 0 and 3 post infection. Administration of CpG ODN fma1555 three days before infection resulted in improved immunoprotection (60–70% survival). Moreover, co-administration of CpG ODN fma1555 and CpG ODN 1555 in this model increased the window for therapeutic treatment against Tacaribe virus infection, and thus supports the use of thermolytic oligonucleotides as prodrugs in the effective treatment of infectious diseases. 相似文献
1000.