全文获取类型
收费全文 | 623篇 |
免费 | 27篇 |
国内免费 | 1篇 |
出版年
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2018年 | 10篇 |
2017年 | 4篇 |
2016年 | 7篇 |
2015年 | 14篇 |
2014年 | 26篇 |
2013年 | 49篇 |
2012年 | 39篇 |
2011年 | 37篇 |
2010年 | 17篇 |
2009年 | 23篇 |
2008年 | 36篇 |
2007年 | 40篇 |
2006年 | 32篇 |
2005年 | 67篇 |
2004年 | 45篇 |
2003年 | 41篇 |
2002年 | 45篇 |
2001年 | 5篇 |
2000年 | 6篇 |
1999年 | 7篇 |
1998年 | 10篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 10篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有651条查询结果,搜索用时 281 毫秒
51.
Yamamoto M Kamata T DO ND Adachi Y Kinjo M Ando T 《Bioscience, biotechnology, and biochemistry》2007,71(11):2860-2863
Female moths of Lyclene dharma dharma (Arctiidae, Lithosiinae) produced three pheromone components (I-III), which strongly stimulated male antennae. Using GC-MS analysis and chemical derivatizations, the following structures were estimated: 6-methyl-2-octadecanone (I), 14-methyl-2-octadecanone (II), and 6,14-dimethyl-2-octadecanone (III). While the stereochemistry of the chiral centers could not be determined because it was difficult to collect a sufficient amount of the natural pheromone, the plain structures of I and II were confirmed by synthesis of the racemic mixtures starting from diols. These methyl-branched ketones have not been identified as a natural product, indicating that they constitute a new chemical group of lepidopteran female sex pheromones. 相似文献
52.
Miyazawa Atsuhiro Kanahara Nobuhisa Kogure Masanobu Otsuka Ikuo Okazaki Satoshi Watanabe Yoshinori Yamasaki Fumiaki Nakata Yusuke Oda Yasunori Hishimoto Akitoyo Iyo Masaomi 《Molecular biology reports》2022,49(3):2015-2024
Molecular Biology Reports - GABAergic system dysfunction has been implicated in the etiology of schizophrenia and of cognitive impairments in particular. Patients with treatment-resistant... 相似文献
53.
Onishi M Inoue M Araki T Iwabuchi H Sagara Y 《Bioscience, biotechnology, and biochemistry》2011,75(2):261-267
The potent odorants in the crust and crumb of white bread were identified and quantified by gas chromatography-mass spectrometry and gas chromatography/olfactometry. The weight loss ratio of the samples baked at 220 °C was controlled in the range of 0-28%. The odorants were classified into 5 types by the transfer characteristics: i) All amounts of odorant transferred from the crust to external space (type-I). ii) All transferred from the crust to the crumb and external space (type-II). iii) Certain amount remaining in the crust and the rest transferred to the crumb and external space (type-III). iv) All transferred from the crumb to external space (type-IV). v) Certain amount remaining in the crumb and the rest transferred to the crust and external space (type-V). The odorants of type-IV were not apparent after the crust had formed. The results indicate that the crust could be a barrier to prevent the odorants from being transferred to external space. 相似文献
54.
Wang X Morales AR Urakami T Zhang L Bondar MV Komatsu M Belfield KD 《Bioconjugate chemistry》2011,22(7):1438-1450
A two-photon absorbing (2PA) and aggregation-enhanced near-infrared (NIR) emitting pyran derivative, encapsulated in and stabilized by silica nanoparticles (SiNPs), is reported as a nanoprobe for two-photon fluorescence microscopy (2PFM) bioimaging that overcomes the fluorescence quenching associated with high chromophore loading. The new SiNP probe exhibited aggregate-enhanced emission producing nearly twice as strong a signal as the unaggregated dye, a 3-fold increase in two-photon absorption relative to the DFP in solution, and approximately 4-fold increase in photostability. The surface of the nanoparticles was functionalized with a folic acid (FA) derivative for folate-mediated delivery of the nanoprobe for 2PFM bioimaging. Surface modification of SiNPs with the FA derivative was supported by zeta potential variation and (1)H NMR spectral characterization of the SiNPs as a function of surface modification. In vitro studies using HeLa cells expressing a folate receptor (FR) indicated specific cellular uptake of the functionalized nanoparticles. The nanoprobe was demonstrated for FR-targeted one-photon in vivo imaging of HeLa tumor xenograft in mice upon intravenous injection of the probe. The FR-targeting nanoprobe not only exhibited highly selective tumor targeting but also readily extravasated from tumor vessels, penetrated into the tumor parenchyma, and was internalized by the tumor cells. Two-photon fluorescence microscopy bioimaging provided three-dimensional (3D) cellular-level resolution imaging up to 350 μm deep in the HeLa tumor. 相似文献
55.
Mammalian germ cells undergo global reprogramming of DNA methylation during their development. Global DNA demethylation occurs around the time when the primordial germ cells colonize the embryonic gonads and this coincides with dynamic changes in chromatin composition. Global de novo DNA methylation takes place with remarkably different dynamics between the two sexes, prospermatogonia attaining methylation during fetal stages and oocytes attaining methylation postnatally. Our hypothesis was that dynamic changes in chromatin composition may precede or accompany the wave of global DNA de novo methylation as well. We used immunocytochemistry to measure global DNA methylation and chromatin components in male and female mouse fetal germ cells compared to control somatic cells of the gonad. We found that global DNA methylation levels sharply increased in male germ cells at 17.5 days post coitum, but remained low in female germ cells at all fetal stages. Global changes in chromatin composition: i, preceded global DNA methylation in fetal germ cells; ii, sex specifically occurred in male but not in female germ cells; iii, affected active and repressive histone marks and iv, included histone tail and histone globular domain modifications. Our data suggest that dynamic changes of chromatin composition may provide a framework for the pattern of male-specific de novo DNA methylation in prospermatogonia. 相似文献
56.
Seiza is a Japanese traditional floor sitting style, sitting down with both legs set at about a 180 degree angle and both femurs on both lower legs. We examined the influence of the somatic dysesthesia and decrease in voluntary toe flexion strength (VTF) induced by Seiza on the center of pressure (COP) sway. Fifteen adults participated in this experiment. COP Sway was measured immediately after a chair resting (pre-test), when a plantar dysethesia occurred (post-test A), and when a decrease (under 30% of maximal voluntary contraction (MVC)) in the VTF set in (post-test B). Tissue oxygenation kinetics in the soleus muscle and plantar somatosensory thresholds (ST) were measured just before each COP test and during Seiza. From starting Seiza, oxygenated hemoglobin/myoglobin decreased markedly and reached a plateau within about 6 min. ST abruptly increased at about 19 min from starting Seiza. VTF decreased to less than 30% MVC in 33% of the participants after 10 min from the acute increase in ST, and in 100% after 20 min. When sustaining Seiza for 19 min, ST rose and sway velocity and antero-posterior sway increased. With continued Seiza, VTF decreased to below 30% MVC at 10 - 20 min, and the above stated body sway further markedly increase. 相似文献
57.
Mevastatin induces apoptosis in HL60 cells dependently on decrease in phosphorylated ERK 总被引:1,自引:0,他引:1
Nishida S Matsuoka H Tsubaki M Tanimori Y Yanae M Fujii Y Iwaki M 《Molecular and cellular biochemistry》2005,269(1-2):109-114
Mevastatin which is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, suppress cell proliferation and induce apoptosis. However, the molecular mechanism of apoptosis induction is not well understood. So, in the present study, we attempted to clarify the mechanism by which mevastatin induces apoptosis in HL60 cells. It was found that mevastatin induced apoptosis. At that time, we observed an increase in caspase-3 activity and morphological fragmentation of the nuclei. The apoptosis induced by mevastatin was not inhibited by the addition of farnesyl pyrophosphate (FPP), squalene, ubiquinone, and isopentenyladenine, but was inhibited by the addition of geranylgeranyl pyrophosphate (GGPP). When we examined the survival signals at the time of apoptotic induction, we also observed that the administration of mevastatin had caused a remarkable decrease in the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). However, other survival signals, such as nuclear factor kappa B (NF-kappaB), protein kinase B (Akt), and p38 mitogen-activated protein kinase (p38), exhibited no change. In addition, no quantitative change was observed in Bcl-2, which was an anti-apoptosis protein. It was also observed that apoptosis was induced when U0126, an MEK inhibitor, was added to the cells to inhibit ERK. These results suggested that mevastatin induced apoptosis when it inhibited GGPP biosynthesis and consequently decreased the level of phosphorylated ERK, which was a survival signal; moreover, at that time, there was no influence on NF-kappaB, Akt, p38, and Bcl-2. The results of this study also suggested that mevastatin could be used as an anticancer agent. 相似文献
58.
Mevastatin induces apoptosis in HL60 cells dependently on decrease in phosphorylated ERK 总被引:2,自引:0,他引:2
Shozo?NishidaEmail author Hiroshi?Matsuoka Masanobu?Tsubaki Yoshihiro?Tanimori Masasi?Yanae Yoshiki?Fujii Masahiro?Iwaki 《Molecular and cellular biochemistry》2005,269(1):109-114
Mevastatin which is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, suppress cell proliferation and induce apoptosis. However, the molecular mechanism of apoptosis induction is not well understood. So, in the present study, we attempted to clarify the mechanism by which mevastatin induces apoptosis in HL60 cells. It was found that mevastatin induced apoptosis. At that time, we observed an increase in caspase-3 activity and morphological fragmentation of the nuclei. The apoptosis induced by mevastatin was not inhibited by the addition of farnesyl pyrophosphate (FPP), squalene, ubiquinone, and isopentenyladenine, but was inhibited by the addition of geranylgeranyl pyrophosphate (GGPP). When we examined the survival signals at the time of apoptotic induction, we also observed that the administration of mevastatin had caused a remarkable decrease in the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). However, other survival signals, such as nuclear factor kappa B (NF-B), protein kinase B (Akt), and p38 mitogen-activated protein kinase (p38), exhibited no change. In addition, no quantitative change was observed in Bcl-2, which was an anti-apoptosis protein. It was also observed that apoptosis was induced when U0126, an MEK inhibitor, was added to the cells to inhibit ERK. These results suggested that mevastatin induced apoptosis when it inhibited GGPP biosynthesis and consequently decreased the level of phosphorylated ERK, which was a survival signal; moreover, at that time, there was no influence on NF-B, Akt, p38, and Bcl-2. The results of this study also suggested that mevastatin could be used as an anticancer agent. (Mol Cell Biochem 269: 109–114, 2005) 相似文献
59.
Okada E Yamazaki M Tanabe M Takeuchi T Nanno M Oshima S Okamoto R Tsuchiya K Nakamura T Kanai T Hibi T Watanabe M 《American journal of physiology. Gastrointestinal and liver physiology》2005,288(4):G745-G754
We have previously demonstrated that mucosal CD4(+) T cells expressing high levels of IL-7 receptor (IL-7R(high)) are pathogenic cells responsible for chronic colitis. Here we investigate whether IL-7 is directly involved in the expansion of IL-7R(high) memory CD4(+) mucosal T cells and the exacerbation of colitis. We first showed that CD4(+) lamina propria lymphocytes (LPLs) from wild-type, T cell receptor-alpha-deficient (TCR-alpha(-/-)), and recombinase-activating gene (RAG)-2(-/-)-transferred mice with or without colitis showed phenotypes of memory cells, but only CD4(+) LPLs from colitic mice showed IL-7R(high). In vitro stimulation by IL-7, but not by IL-15 and thymic stromal lymphopoietin, enhanced significant proliferative responses and survival of colitic CD4(+), but not normal CD4(+) LPLs. Importantly, in vivo administration of IL-7 mice accelerated the expansion of IL-7R(high) memory CD4(+) LPLs and thereby exacerbated chronic colitis in RAG-2(-/-) mice transferred with CD4(+) LPLs from colitic TCR-alpha(-/-) mice. Conversely, the administration of anti-IL-7R monoclonal antibody significantly inhibited the development of TCR-alpha(-/-) colitis with decreased expansion of CD4(+) LPLs. Collectively, the present data indicate that IL-7 is essential for the expansion of pathogenic memory CD4(+) T cells under pathological conditions. Therefore, therapeutic approaches targeting the IL-7R pathway may be feasible in the treatment of human inflammatory bowel disease. 相似文献
60.