全文获取类型
收费全文 | 1586篇 |
免费 | 68篇 |
国内免费 | 4篇 |
专业分类
1658篇 |
出版年
2022年 | 6篇 |
2021年 | 9篇 |
2020年 | 13篇 |
2019年 | 17篇 |
2018年 | 19篇 |
2017年 | 28篇 |
2016年 | 31篇 |
2015年 | 45篇 |
2014年 | 62篇 |
2013年 | 94篇 |
2012年 | 110篇 |
2011年 | 116篇 |
2010年 | 67篇 |
2009年 | 66篇 |
2008年 | 96篇 |
2007年 | 114篇 |
2006年 | 90篇 |
2005年 | 120篇 |
2004年 | 98篇 |
2003年 | 97篇 |
2002年 | 89篇 |
2001年 | 31篇 |
2000年 | 20篇 |
1999年 | 23篇 |
1998年 | 26篇 |
1997年 | 13篇 |
1996年 | 13篇 |
1995年 | 14篇 |
1994年 | 10篇 |
1993年 | 11篇 |
1992年 | 8篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 8篇 |
1988年 | 10篇 |
1987年 | 14篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 7篇 |
1983年 | 9篇 |
1982年 | 9篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1967年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有1658条查询结果,搜索用时 0 毫秒
991.
Ishii T Shiomi Y Takami T Murakami Y Ohnishi N Nishitani H 《The Journal of biological chemistry》2010,285(53):41993-42000
The licensing factor Cdt1 is degraded by CRL4(Cdt2) ubiquitin ligase dependent on proliferating cell nuclear antigen (PCNA) during S phase and when DNA damage is induced in G(1) phase. Association of both Cdt2 and PCNA with chromatin was observed in S phase and after UV irradiation. Here we used a micropore UV irradiation assay to examine Cdt2 accumulation at cyclobutane pyrimidine dimer-containing DNA-damaged sites in the process of Cdt1 degradation in HeLa cells. Cdt2, present in the nucleus throughout the cell cycle, accumulated rapidly at damaged DNA sites during G(1) phase. The recruitment of Cdt2 is dependent on prior PCNA chromatin binding because Cdt2 association was prevented when PCNA was silenced. Cdt1 was also recruited to damaged sites soon after UV irradiation through its PIP-box. As Cdt1 was degraded, the Cdt2 signal at damaged sites was reduced, but PCNA, cyclobutane pyrimidine dimer, and XPA (xeroderma pigmentosum, complementation group A) signals remained at the same levels. These findings suggest that Cdt1 degradation following UV irradiation occurs rapidly at damaged sites due to PCNA chromatin loading and the recruitment of Cdt1 and CRL4(Cdt2), before DNA damage repair is completed. 相似文献
992.
993.
Shibayama-Imazu T Sonoda I Sakairi S Aiuchi T Ann WW Nakajo S Itabe H Nakaya K 《Apoptosis : an international journal on programmed cell death》2006,11(9):1535-1543
We reported previously that vitamin K2 selectively induces apoptosis in human ovary cancer cells (TYK-nu cells) and pancreatic cancer cells (MIA PaCa-2 cells) through
a mitochondrion-dependent pathway. In the present study, we examined the details of the mechanism of vitamin K2-induced apoptosis in TYK-nu cells. We found that superoxide (O2
•−) was produced by TYK-nu cells between 2 and 3 days after the start of treatment with vitamin K2, whereas it was produced within 30 min after the start of treatment with geranylgeraniol. The vitamin K2-induced apoptosis was inhibited by anti-oxidants, such as α-tocopherol, Tiron and N-acetyl-L-cysteine (NAC). Furthermore,
both the production of superoxide and the induction of apoptosis by vitamin K2 were inhibited almost completely by cycloheximide, an inhibitor of protein synthesis, suggesting that the synthesis of enzymes
for the production of superoxide might be required for these processes. In parallel with the production of superoxide, the
mitochondrial transmembrane potential, as measured by staining with Mitotracker Red CMXRos, dissipated during treatment of
TYK-nu cells with vitamin K2 for 3 days. The vitamin K2-induced depolarization of mitochondrial membranes was completely inhibited by α-tocopherol and, to a lesser extent, by Tiron
and NAC. Since α-tocopherol reacts with oxygen radicals, such as superoxide, within the hydrophobic environment of the mitochondrial
membrane, we postulate that vitamin K2-induced oxidative stress in mitochondria might damage mitochondrial membranes, with subsequent release of cytochrome c, the activation of procaspase 3 and, eventually, apoptosis. 相似文献
994.
Takahashi S Ogasawara H Hiwatashi K Hori K Hata K Tachibana T Itoh Y Sugiyama T 《Journal of biochemistry》2006,139(2):197-202
We discovered and characterized a novel type D-aspartyl endopeptidase (DAEP) produced extracellularly by Paenibacillus sp. B38. This bacterial DAEP of M(r) 34,798 (named paenidase) appeared to be converted into a smaller form of M(r) 34,169 by the proteolytic removal of 5 amino acid residues from the N-terminal. The intact and modified forms of the enzyme displayed essentially the same enzymatic properties. The enzyme specifically hydrolyzed succinyl-D-aspartic acid alpha-(p-nitroanilide) and succinyl-D-aspartic acid alpha-(4-methylcoumaryl-7-amide) to generate p-nitroaniline and 7-amino-4-methylcoumarin, and internally cleaved a synthetic peptide (D-A-E-F-R-H-[D-Asp]-G-S-Y) of the [D-Asp](7) amyloid beta (Abeta) protein between [D-Asp](7)-G(8). Either was totally inert to the normal Abeta peptide sequence containing L-Asp, instead of D-Asp at the 7th position. Thus, paenidase is the first DAEP from a microorganism that specifically recognizes an internal D-Asp residue to cleave [D-Asp]-X peptide bonds. 相似文献
995.
Sakiyama H Takahashi M Yamamoto T Teshima T Lee SH Miyamoto Y Misonou Y Taniguchi N 《Journal of biochemistry》2006,139(2):245-253
3-Deoxyglucosone (3-DG), a dicarbonyl compound produced by glycation, plays a role in the modification and cross-linking of long-lived proteins. We synthesized [3H]3-DG from [3H]glucose and developed an internalization assay system using HPLC to examine its cellular metabolism. When smooth muscle cells or human umbilical vein endothelial cells were incubated with [3H]3-DG, it was found that [3H]3-DG was internalized by cells in a time dependent manner. The rate of internalization was reduced when the cells were incubated at 4 degrees C or treated with phenylarsine oxide (PAO). By monitoring [3H]3-DG taken up by cells, it was confirmed that 3-DG is reduced to 3-deoxyfructose (3-DF) and that this reaction was inhibited by an aldo-keto reductase inhibitor (ARI). The presence of 3-DG led to an increase in reactive oxygen species levels in the cells and subsequent apoptosis, and the effect was enhanced by pretreatment with ARI. These results suggest that 3-DG is internalized by cells and reduced to 3-DF by aldo-keto reductases, and that the internalized 3-DG is responsible for the production of intracellular oxidative stress. 相似文献
996.
997.
Kato R Maeda T Akaike T Tamai I 《American journal of physiology. Endocrinology and metabolism》2006,290(5):E968-E975
In the testis, nucleosides and nucleobases are important substrates of the salvage pathway for nucleotide biosynthesis, and one of the roles of Sertoli cells is to provide nutrients and metabolic precursors to spermatogenic cells located within the blood-testis barrier (BTB). We have already shown that concentrative and equilibrative nucleoside transporters are expressed and are functional in primary-cultured rat Sertoli cells as a BTB model, but little is known about nucleobase transport at the BTB or about the genes encoding specific nucleobase transporters in mammalian cells. In the present study, we examined the uptake of purine ([3H]guanine) and pyrimidine ([3H]uracil) nucleobases by primary-cultured rat Sertoli cells. The uptake of both nucleobases was time and concentration dependent. Kinetic analysis showed the involvement of three different transport systems in guanine uptake. In contrast, uracil uptake was mediated by a single Na+-dependent high-affinity transport system. Guanine uptake was inhibited by other purine nucleobases but not by pyrimidine nucleobases, whereas uracil uptake was inhibited only by pyrimidine nucleobases. In conclusion, it was suggested that there might be purine- or pyrimidine-selective nucleobase transporters in rat Sertoli cells. 相似文献
998.
角蒿总生物碱提取工艺的研究 总被引:3,自引:0,他引:3
本文的目的是利用正交试验设计优选渗滤法提取角蒿有效成分的工艺条件。以角蒿酯碱的含量为指标,通过L9(3^4)t交试验设计,对提取工艺的溶媒浓度、溶媒用量和渗滤速度3个因素进行优选研究,以筛选出角蒿的最佳提取工艺条件。试验结果表明影响提取的主次因素为:溶媒用量〉溶媒浓度〉渗滤速度。优选得到的最佳提取工艺条件是用25倍量0.2%盐酸渗漉提取,渗滤速度为7mL/min,且工艺条件稳定可行。 相似文献
999.
The kinetics of the complexation of Ni(II) with 1,10-phenanthroline(phen), 4,7-dimethyl-1,10-phenanthroline(dmphen), and 5-nitro-1,10-phenanthroline(NO2phen) in acetonitrile-water mixed solvents of acetonitrile mole fraction xAN = 0, 0.05, 0.1, 0.2 and 0.3 at 288, 293, 298 and 303 K have been studied by stopped-flow method at ionic strength of 1.0 (NaClO4) and pH 7.4. The corresponding activation enthalpy, entropy, and free energy were determined from the observed rate constants. The complexation of Ni(II) with the three ligands has comparable observed rate constants; in pure water the observed rate constants are (×103 dm3 mol−1 s−1) 2.31, 2.57, and 1.38 for phen, dmphen and NO2phen, respectively. The corresponding activation parameters for the three ligands are, however, considerably different; in pure water the ΔH‡/ΔS‡ (kJ mol−1/J K−1 mol−1) are 44.7/−30.2, 19.5/−114.1, and 32.2/−76.9 for phen, dmphen, and NO2phen, respectively. The effects of solvent composition on the kinetics are also markedly different for the three ligands. The ΔH‡ and ΔS‡ showed a minimum at xAN = 0.1 for phen; for dmphen and NO2phen, however, maxima at xAN = 0.2 were observed. Nevertheless, there is an effective enthalpy-entropy compensation for the ΔH‡/ΔS‡ of all the three ligands, demonstrating the significant effects of the changes in solvation and solvent structure on the complexation kinetics. As the rate-determining step of Ni(II) complexation is the dissociation of a water molecule from Ni(II), the solvent and ligand dependencies in the Ni(II) complexation kinetics are ascribed to the change in solvation status of the ligands and the altered solvent structures upon changing solvent composition. 相似文献
1000.
Jin H Yoshitake H Tsukamoto H Takahashi M Mori M Takizawa T Takamori K Ogawa H Kinoshita K Araki Y 《Zygote (Cambridge, England)》2006,14(3):201-208
TEX101, a glycoprotein we recently identified, is primarily characterized as a unique germ-cell-specific marker protein that shows sexually dimorphic expression during mouse gonad development. Based on data obtained from molecular biological as well as immuno-morphological studies, we believe this molecule may play a role in the process underlying germ cell formation. However, many points remain unclear as the molecular characteristics and its physiological functions are far from being completely understood. To clarify the molecular basis of TEX101, we herein report a further biochemical characterization of the molecule using testicular Triton X-100 extracts from mice. Deglycosylation studies using endoglycohydrolases that delete N-linked oligosaccharides (OS) from the molecule show that TEX101 is highly (approximately 47%) N-glycosylated. All potential N-glycosylation sites within TEX101 are glycosylated and most of these sites are occupied by endoglycosidase F2-sensitive biantennary complex type OS units. In addition, an extremely low population among TEX101 possesses only endoglycosidase H-sensitive hybrid type OS units. In studies using phosphatidylinositol-specific phospholipase C against native testicular cells or TEX101 transfectant, the enzyme treatment caused major reduction of the TEX101 expression on the cell, suggesting that TEX101, at least in part, is expressed as a glycosylphosphatidylinositol-anchored protein. Taken together, these findings will help elucidate the molecular nature of TEX101, a marker molecule that appeared on germ cells during gametogenesis. 相似文献