全文获取类型
收费全文 | 2533篇 |
免费 | 289篇 |
出版年
2023年 | 8篇 |
2022年 | 26篇 |
2021年 | 60篇 |
2020年 | 29篇 |
2019年 | 60篇 |
2018年 | 70篇 |
2017年 | 55篇 |
2016年 | 98篇 |
2015年 | 138篇 |
2014年 | 134篇 |
2013年 | 146篇 |
2012年 | 214篇 |
2011年 | 170篇 |
2010年 | 141篇 |
2009年 | 104篇 |
2008年 | 138篇 |
2007年 | 141篇 |
2006年 | 117篇 |
2005年 | 111篇 |
2004年 | 113篇 |
2003年 | 78篇 |
2002年 | 92篇 |
2001年 | 30篇 |
2000年 | 49篇 |
1999年 | 36篇 |
1998年 | 29篇 |
1997年 | 16篇 |
1996年 | 29篇 |
1995年 | 17篇 |
1994年 | 33篇 |
1993年 | 19篇 |
1992年 | 26篇 |
1991年 | 24篇 |
1990年 | 24篇 |
1989年 | 21篇 |
1988年 | 16篇 |
1987年 | 13篇 |
1986年 | 15篇 |
1985年 | 19篇 |
1984年 | 13篇 |
1983年 | 10篇 |
1982年 | 11篇 |
1980年 | 16篇 |
1977年 | 12篇 |
1976年 | 11篇 |
1974年 | 8篇 |
1973年 | 8篇 |
1972年 | 10篇 |
1969年 | 9篇 |
1967年 | 7篇 |
排序方式: 共有2822条查询结果,搜索用时 115 毫秒
1.
Cristian A. Acevedo Elizabeth Y. Sanchez Juan G. Reyes Manuel E. Young 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(3-4):449-455
It is known that skin releases volatile organic compounds to the environment, and also that its emission pattern changes with aging of the skin. It could be considered, that these compounds are intermediaries in cell metabolism, since many intermediaries of metabolic pathways have a volatile potential. In this work, a simple and non-destructive method consisting of SPME sampling and GC/MS analysis was developed to identify volatile organic emanations from cell cultures. This technique, applied to skin cells culture, indicates that the cells or cell metabolism produce several skin emissions. Chemometric analysis was performed in order to explore the relationship between a volatile profile and the senescence of cell cultures. Volatile profiles were different for cell cultures in different degrees of senescence, indicating that volatile compound patterns could be used to provide information about the age of skin cells. 相似文献
2.
Amiloride fluxes across erythrocyte membranes 总被引:3,自引:0,他引:3
Amiloride is known to inhibit both the influx of Na+ and the activation of mitogenesis in many cultured cell lines. This paper describes experiments in which the permeability coefficient of amiloride was determined from measurements of tracer fluxes across human erythrocytes and resealed ghosts. From an analysis of these fluxes, a permeability coefficient of 10(-7) cm/s for the uncharged form of amiloride was deduced. Based upon this measured permeability value, we present calculations of intracellular accumulation times of amiloride in cells of differing surface-to-volume ratio. 相似文献
3.
Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress 总被引:3,自引:0,他引:3
4.
Bone Cell-autonomous Contribution of Type 2 Cannabinoid Receptor to Breast Cancer-induced Osteolysis
Antonia Sophocleous Silvia Marino John G. Logan Patrick Mollat Stuart H. Ralston Aymen I. Idris 《The Journal of biological chemistry》2015,290(36):22049-22060
The cannabinoid type 2 receptor (CB2) has previously been implicated as a regulator of tumor growth, bone remodeling, and bone pain. However, very little is known about the role of the skeletal CB2 receptor in the regulation of osteoblasts and osteoclasts changes associated with breast cancer. Here we found that the CB2-selective agonists HU308 and JWH133 reduced the viability of a variety of parental and bone-tropic human and mouse breast cancer cells at high micromolar concentrations. Under conditions in which these ligands are used at the nanomolar range, HU308 and JWH133 enhanced human and mouse breast cancer cell-induced osteoclastogenesis and exacerbated osteolysis, and these effects were attenuated in cultures obtained from CB2-deficient mice or in the presence of a CB2 receptor blocker. HU308 and JWH133 had no effects on osteoblast growth or differentiation in the presence of conditioned medium from breast cancer cells, but under these circumstances both agents enhanced parathyroid hormone-induced osteoblast differentiation and the ability to support osteoclast formation. Mechanistic studies in osteoclast precursors and osteoblasts showed that JWH133 and HU308 induced PI3K/AKT activity in a CB2-dependent manner, and these effects were enhanced in the presence of osteolytic and osteoblastic factors such as RANKL (receptor activator of NFκB ligand) and parathyroid hormone. When combined with published work, these findings suggest that breast cancer and bone cells exhibit differential responses to treatment with CB2 ligands depending upon cell type and concentration used. We, therefore, conclude that both CB2-selective activation and antagonism have potential efficacy in cancer-associated bone disease, but further studies are warranted and ongoing. 相似文献
5.
6.
7.
Characterization of adenine phosphoribosyltransferase from the human malaria parasite, Plasmodium falciparum 总被引:2,自引:0,他引:2
Because of their inability to synthesize purines de novo, malaria parasites rely on purine phosphoribosyltransferases (PRTases) to convert purine bases salvaged from the host cell (the erythrocyte) into the corresponding purine nucleoside monophosphates. Our studies with late trophozoites of the human malaria parasite, Plasmodium falciparum, showed that virtually all of the purine PRTase activity is accounted for by two distinct enzymes. One enzyme utilizes hypoxanthine, guanine and xanthine (Queen, S.A., Vander Jagt, D. and Reyes, P. (1988) Mol. Biochem. Parasitol. 30, 123-134). The second enzyme utilizes only adenine and is the subject of this paper. This latter enzyme exhibits a biphasic pH-activity profile and is moderately to weakly inhibited by several divalent metal ions. Several of the properties of the P. falciparum enzyme were found to differ significantly from those of human erythrocyte adenine PRTase. (1) The molecular weight (18,000) of the parasite enzyme is smaller than that of the host cell enzyme. (2) The parasite enzyme, unlike the erythrocyte enzyme, is not significantly inhibited by sulfhydryl reagents. (3) 6-Mercaptopurine and 2,6-diaminopurine proved to be competitive inhibitors of the parasite enzyme (Ki 0.70 and 1.0 mM, respectively); on the other hand, the human enzyme is not inhibited by these agents. (4) The Km for adenine (0.80 microM) and 5-phosphoribosyl-1-pyrophosphate (0.70 microM) displayed by the parasite enzyme are significantly smaller than the corresponding Km values shown by the erythrocyte enzyme. These distinctions between the parasite and host enzymes point to the possibility that adenine PRTase of P. falciparum may represent a potential target for chemotherapeutic attack. 相似文献
8.
Acid and alkaline phosphatase activities in culture liquid and mycelial extract during autolysis were studied in seven fungi of the general Ascomycotina, Basidiomycotina and Zygomycotina. High activities of extracellular and mycelial extract acid phosphatase and lower activities of alkaline phosphatase were found in Ascomycotina, and acid phosphatase was present in Basidiomycotina. In Zygomycotina only mycelial extract alkaline phosphatase activity was detected. A correlation between degree of autolysis, pH and acid phosphatase activity was demonstrated. 相似文献
9.
Induction of vancomycin resistance in Enterococcus faecium by inhibition of transglycosylation 总被引:6,自引:0,他引:6
Vancomycin resistance has recently been recognized among clinical isolates of enterococci. Resistance is inducible, and associated with production of a novel 39 kDa membrane protein. The mechanism by which exposure to vancomycin, which does not penetrate the cell membrane, induces resistance is unknown. In the vancomycin resistant strain Enterococcus faecium 228, resistance was also inducible by moenomycin, suggesting that inhibition of the transglycosylation step in peptidoglycan synthesis may be required for induction of resistance. Cytoplasmic pools of peptidoglycan precursors were increased after exposure to vancomycin or moenomycin, representing a potential means for regulation of induction. 相似文献
10.
Pectic activity in autolyzed cultures of Botrytis cinerea in a medium with and without pectin was similar, but in the medium with pectin maximal activities occurred in younger cultures. The pectic activities found were polygalacturonase, polymethylgalacturonase, endo activity (pectin as substrate) and pectin lyase. The molecular weights of polygalacturonase, polymethylgalacturonase and endo activity (pectin as substrate) were 36000, 33000 and 30200 daltons respectively, and the molecular weight of pectin lyase was 18200 daltons. By gel electrophoresis four different pectic activities were detected, three in the top of the gel and one in the bottom. Two enzymes were characterized, the polygalacturonase activity (first band in the top) inhibited by Ca++ and the pectin lyase activity (in the bottom) which was not inhibited by Ca++. These enzymes are not induced by the presence of pectin in the medium during degradation of Botrytis cinerea. 相似文献