全文获取类型
收费全文 | 347篇 |
免费 | 19篇 |
出版年
2022年 | 5篇 |
2021年 | 5篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 12篇 |
2017年 | 5篇 |
2016年 | 8篇 |
2015年 | 18篇 |
2014年 | 19篇 |
2013年 | 23篇 |
2012年 | 26篇 |
2011年 | 23篇 |
2010年 | 17篇 |
2009年 | 19篇 |
2008年 | 25篇 |
2007年 | 16篇 |
2006年 | 20篇 |
2005年 | 12篇 |
2004年 | 14篇 |
2003年 | 15篇 |
2002年 | 11篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1970年 | 2篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 4篇 |
1965年 | 1篇 |
1963年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有366条查询结果,搜索用时 15 毫秒
21.
Nae Takizawa Susumu Tanaka Koshiro Nishimoto Yuki Sugiura Makoto Suematsu Chisato Ohe Haruyuki Ohsugi Yosuke Mizuno Kuniaki Mukai Tsugio Seki Kenji Oki Celso E. Gomez-Sanchez Tadashi Matsuda 《Current issues in molecular biology》2022,44(1):128
Primary aldosteronism is most often caused by aldosterone-producing adenoma (APA) and bi-lateral adrenal hyperplasia. Most APAs are caused by somatic mutations of various ion channels and pumps, the most common being the inward-rectifying potassium channel KCNJ5. Germ line mutations of KCNJ5 cause familial hyperaldosteronism type 3 (FH3), which is associated with severe hyperaldosteronism and hypertension. We present an unusual case of FH3 in a young woman, first diagnosed with primary aldosteronism at the age of 6 years, with bilateral adrenal hyperplasia, who underwent unilateral adrenalectomy (left adrenal) to alleviate hyperaldosteronism. However, her hyperaldosteronism persisted. At the age of 26 years, tomography of the remaining adrenal revealed two different adrenal tumors, one of which grew substantially in 4 months; therefore, the adrenal gland was removed. A comprehensive histological, immunohistochemical, and molecular evaluation of various sections of the adrenal gland and in situ visualization of aldosterone, using matrix-assisted laser desorption/ionization imaging mass spectrometry, was performed. Aldosterone synthase (CYP11B2) immunoreactivity was observed in the tumors and adrenal gland. The larger tumor also harbored a somatic β-catenin activating mutation. Aldosterone visualized in situ was only found in the subcapsular regions of the adrenal and not in the tumors. Collectively, this case of FH3 presented unusual tumor development and histological/molecular findings. 相似文献
22.
Phosphorylation of Rab proteins from the brain of Bombyx mori 总被引:1,自引:0,他引:1
Rab proteins play fundamental roles in the regulation of membrane traffic. Previously, from the brain of Bombyx mori we isolated two cDNA clones (BRab1 and BRab14), each of which encoded a different member of Rab-protein family and was expressed in Escherichia coli and purified using an affinity chromatography. In this study, one cDNA clone (BRab8) was isolated from a cDNA library from the brain of B. mori. The recombinant protein was expressed in E. coli and purified. Next, the phosphorylations of these three purified BRab proteins were examined, using mammalian protein kinases in vitro. Protein kinase C (PKC) phosphorylated BRab8 and BRab14 proteins. Protein kinase A faintly phosphorylated BRab8 and BRab14 proteins. Calcium/calmodulin-dependent protein kinase faintly phosphorylated BRab8 protein. Next, brains of B. mori were dissected and homogenized. The homogenate showed a calcium-dependent protein kinase activity of BRab8 and BRab14 proteins. So PKC from the brain of B. mori was partially purified by a sequence of chromatographies on DEAE-Cellulofine and affinity chromatography. This PKC phosphorylated BRab8 and BRab14 proteins. These results suggest that the function of Rab proteins in the brain of B. mori is regulated by calcium-dependent protein kinases. 相似文献
23.
24.
25.
Hexokinase is the first enzyme involved in the glycolysis process that produces glucose phosphorylate. Our previous study reported on our cloning of mouse Hk1-s (mHk1-s) cDNA, which were expressed only in testis cells, and noted that this cDNA has a spermatogenic cell-specific region (SSR) that replaces the porin binding domain (PBD) in the Hk1of somatic cells. Although we know that PBD binds to the outer membrane of a mitochondrion, the role of the SSR is not yet understood. To investigate the intracellular localization of SSR, we constructed expression vectors with the epitope tag (GFP-, HA-), subcloned SSR, or PBD cDNA. We transfected these vectors in mouse fibroblast, NIH3T3 cells, after which we observed the localization of the SSR and PBD in the NIH3T3 cells. Our current study using the immunocytochemical method revealed that PBD is concentrated around the mitochondrion. However, the SSR could not be ascribed to the mitochondrion, ER, or nuclear colocalization. Moreover, subcellular fractionation analysis showed that PBD was detected in the mitochondrial fraction, and that SSR was detected in the cytosolic fraction. Our findings suggest that PBD of Hk1 targets mitochondrion, but the SSR of mHk1-s targets some specific organellae. 相似文献
26.
Arabis gemmifera is a hyperaccumulator of Cd and Zn 总被引:1,自引:0,他引:1
Hyperaccumulators are essential for phytoremediation of heavy metals. In Europe and North America, many studies have been conducted to find more effective plants for phytoremediation of various pollutants. In Japan, this field of research has just recently come more into focus. A type of fern in Japan, Athyrium yokoscense, is well known as a hyperaccumulator of Cd and Zn. However, it is not suitable for phytoremediation because it is a summer green and grows slowly. Therefore, in order to find hyperaccumulators other than from A. yokoscense, we surveyed plants growing at polluted sites in Japan. We found that the Brassicae Arabis gemmifera is a hyperaccumulator of Cd and Zn, with phytoextraction capacities almost equal to Thlaspi caerulescens. 相似文献
27.
Masuda T Oyama Y Yamamoto N Umebayashi C Nakao H Toi Y Takeda Y Nakamoto K Kuninaga H Nishizato Y Nonaka A 《Bioscience, biotechnology, and biochemistry》2003,67(6):1401-1404
The cytotoxic activity of ethanol extracts from 53 parts of 36 species of medicinal and edible plants cultivated in Okinawa was measured by using K562 human leukemia cells by a flow cytometric method. Two extracts from Rhodea japonica and Hypericum chinense were cytotoxic at a concentration of 10 microg/ml. The main cytotoxic constituent of Rhodea japonica was isolated and identified to be rhodexin A, which has been isolated as a cardetonic agent of the plant. The IC(50) value for rhodexin A against the growth of K562 cells was 19 nM, this activity being much stronger than that of ouabain (IC(50), 60 nM). 相似文献
28.
Kei-ichi Morita Takuya Naruto Kousuke Tanimoto Chisato Yasukawa Yu Oikawa Kiyoshi Masuda Issei Imoto Johji Inazawa Ken Omura Hiroyuki Harada 《PloS one》2015,10(11)
Gorlin syndrome (GS) is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs). In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS) analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs) of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals), whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions. 相似文献
29.
Fumiyuki Nakagawa Katsutaro Morino Satoshi Ugi Atsushi Ishikado Keiko Kondo Daisuke Sato Shiho Konno Ken-ichi Nemoto Chisato Kusunoki Osamu Sekine Akihiro Sunagawa Masanori Kawamura Noriko Inoue Yoshihiko Nishio Hiroshi Maegawa 《Biochemical and biophysical research communications》2014
It has recently been reported that expression of heme oxygenase-1 (HO-1) plays a protective role against many diseases. Furthermore, n-3 polyunsaturated fatty acids (PUFAs) were shown to induce HO-1 expression in several cells in vitro, and in a few cases also in vivo. However, very few reports have demonstrated that n-3 PUFAs induce HO-1 in vivo. 相似文献
30.
Tsubaki M Kato C Manno M Ogaki M Satou T Itoh T Kusunoki T Tanimori Y Fujiwara K Matsuoka H Nishida S 《Molecular and cellular biochemistry》2007,304(1-2):53-60
Osteolytic lesions are rapidly progressive during the terminal stages of myeloma, and the bone pain or bone fracture that
occurs at these lesions decreases the patients’ quality of life to a notable degree. In relation to the etiology of this bone
destruction, it has been reported recently that MIP-1α, produced in large amounts in myeloma patients, acts indirectly on
osteoclastic precursor cells, and activates osteoclasts by way of bone-marrow stromal cells or osteoblasts, although the details
of this process remain obscure. In the present study, our group investigated the mechanism by which RANKL expression is induced
by MIP-1α and the effects of MIP-1α on the activation of osteoclasts. RANKL mRNA and RANKL protein expressions increased in
both ST2 cells and MC3T3–E1 cells in a MIP-1α concentration-dependent manner. RANKL mRNA expression began to increase at 1 h
after the addition of MIP-1α; the increase became remarkable at 2 h, and continuous expression was observed subsequently.
Both ST2 and MC3T3-E1 cells showed similar levels of increased RANKL protein expression at 1, 2, and 3 days after the addition
of MIP-1α. After the addition of MIP-1α, the amount of phosphorylated ERK1/2 and Akt protein expressions showed an increase,
as compared to the corresponding amount in the control group. On the other hand, the amount of phosphorylated p38MAPK protein
expression showed a decrease from the amount in the control group after the addition of MIP-1α. U0126 (a MEK1/2 inhibitor)
or LY294002 (a PI3K inhibitor) was added to ST2 and MC3T3-E1 cells, and was found to inhibit RANKL mRNA and RANKL protein
expression in these cells. When SB203580, a p38MAPK inhibitor, was added, RANKL mRNA and RANKL protein expression were increased
in these cells. MIP-1α was found to promote osteoclastic differentiation of C7 cells, an osteoclastic precursor cell line,
in a MIP-1α concentration-dependent manner. MIP-1α promoted differentiation into osteoclasts more extensively in C7 cells
incubated together with ST2 and MC3T3-E1 cells than in C7 cells incubated alone. These results suggested that MIP-1α directly
acts on the osteoclastic precursor cells and induces osteoclastic differentiation. This substance also indirectly induces
osteoclastic differentiation through the promotion of RANKL expression in bone-marrow stromal cells and osteoblasts. The findings
of this investigation suggested that activation of the MEK/ERK and the PI3K/Akt pathways and inhibition of p38MAPK pathway
were involved in RANKL expression induced by MIP-1α in bone-marrow stromal cells and osteoblasts. This finding may be useful
in the development of an osteoclastic inhibitor that targets intracellular signaling factors. 相似文献