全文获取类型
收费全文 | 2279篇 |
免费 | 119篇 |
出版年
2023年 | 6篇 |
2022年 | 23篇 |
2021年 | 42篇 |
2020年 | 15篇 |
2019年 | 25篇 |
2018年 | 34篇 |
2017年 | 29篇 |
2016年 | 44篇 |
2015年 | 73篇 |
2014年 | 70篇 |
2013年 | 155篇 |
2012年 | 153篇 |
2011年 | 160篇 |
2010年 | 95篇 |
2009年 | 92篇 |
2008年 | 154篇 |
2007年 | 182篇 |
2006年 | 156篇 |
2005年 | 123篇 |
2004年 | 175篇 |
2003年 | 131篇 |
2002年 | 127篇 |
2001年 | 26篇 |
2000年 | 27篇 |
1999年 | 23篇 |
1998年 | 35篇 |
1997年 | 23篇 |
1996年 | 15篇 |
1995年 | 18篇 |
1994年 | 10篇 |
1993年 | 15篇 |
1992年 | 21篇 |
1991年 | 21篇 |
1990年 | 9篇 |
1989年 | 14篇 |
1988年 | 15篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1967年 | 5篇 |
1966年 | 1篇 |
排序方式: 共有2398条查询结果,搜索用时 31 毫秒
71.
Atsushi Suzuki Akihiro Okitani Masao Fujimaki 《Bioscience, biotechnology, and biochemistry》2013,77(4):579-585
Some physicochemical properties of the cathepsin D purified from the rabbit muscle (L. dorsi) were investigated.The sedimentation coefficient (s20,w) and the molecular weight determined from sedimentation equilibrium experiment was 3.83 S and 29,000~30,000, respectively.The amino acid composition of the enzyme was determined with an automatic amino acid analyzer.The proteolytic specificity of the enzyme was also investigated using the B-chain of oxidized beef insulin as the substrate. The cathepsin D cleaved the bonds Phe-Val, Ala-Leu, Leu-Tyr and Tyr-Leu. The specificity of the cathepsin D was fairly similar to that of the pepsin. 相似文献
72.
Akihiro Okitani Yuzuru Otsuka Mamoru Sugitani Masao Fujimaki 《Bioscience, biotechnology, and biochemistry》2013,77(3):573-579
The properties of the neutral proteolytic activity concentrated in a fraction (F–1) separated from rabbit muscle homogenate were examined by measuring the effects of various reagents and metal ions, the time course of the proteolysis and Ca-stability. The obtained results have indicated that F–1 contains two types of neutral protease active on proteins, tentatively named Protease I and II, The former, which is activated by Ca2+ and Ca-labile, shows an explosive production of Cu-Folin phenol reagent positive materials at the early stage of incubation. The latter, which is Ca-stable, shows a large production of ninhydrin positive materials throughout the incubation time. The proteolysis by F–1 was similar to the autolysis of muscle homogenate in all the properties examined. Therefore, Proteases I and II were assumed to be main enzymes responsible for the muscle proteolysis at the neutral pH region. As there has been no factor denying their functioning in living muscle, it is probable that Proteases I and II take important parts in the muscle catabolism. 相似文献
73.
Yusuke K. Kawai Kensuke P. Watanabe Akihiro Ishii Aiko Ohnuma Hirofumi Sawa Yoshinori Ikenaka Mayumi Ishizuka 《Comparative biochemistry and physiology. Part D, Genomics & proteomics》2013,8(3):201-208
The cytochrome P450 (CYP) 1–3 families are involved in xenobiotic metabolism, and are expressed primarily in the liver. Ostriches (Struthio camelus) are members of Palaeognathae with the earliest divergence from other bird lineages. An understanding of genes coding for ostrich xenobiotic metabolizing enzyme contributes to knowledge regarding the xenobiotic metabolisms of other Palaeognathae birds. We investigated CYP1–3 genes expressed in female ostrich liver using a next-generation sequencer. We detected 10 CYP genes: CYP1A5, CYP2C23, CYP2C45, CYP2D49, CYP2G19, CYP2W2, CYP2AC1, CYP2AC2, CYP2AF1, and CYP3A37. We compared the gene expression levels of CYP1A5, CYP2C23, CYP2C45, CYP2D49, CYP2G19, CYP2AF1, and CYP3A37 in ostrich liver and determined that CYP2G19 exhibited the highest expression level. The mRNA expression level of CYP2G19 was approximately 2–10 times higher than those of other CYP genes. The other CYP genes displayed similar expression levels. Our results suggest that CYP2G19, which has not been a focus of previous bird studies, has an important role in ostrich xenobiotic metabolism. 相似文献
74.
Shinji Sato Akihiro Murakami Akiko Kuwajima Kazuhiko Takehara Tsuneyo Mimori Atsushi Kawakami Michiaki Mishima Takafumi Suda Mariko Seishima Manabu Fujimoto Masataka Kuwana 《PloS one》2016,11(4)
ObjectiveAutoantibodies to melanoma differentiation-associated gene 5 (MDA5) are specifically expressed in patients with dermatomyositis (DM) and are associated with a subset of DM patients with rapidly progressive interstitial lung disease (RP-ILD). Here, we examined the clinical utility of a newly developed enzyme-linked immunosorbent assay (ELISA) system for detecting these antibodies.MethodsHere we developed an improved ELISA for detecting anti-MDA5 antibodies. We then performed a multicenter clinical study involving 8 medical centers and enrolled 242 adult patients with polymyositis (PM)/DM, 190 with non-PM/DM connective tissue disease (CTD), 154 with idiopathic interstitial pneumonia (IIP), and 123 healthy controls. Anti-MDA5 antibodies in the patients’ serum samples were quantified using our newly developed ELISA, and the results were compared to those obtained using the gold-standard immunoprecipitation (IP) assay. In addition, correlations between the ELISA-quantified anti-MDA5 antibodies and clinical characteristics were evaluated.ResultsIn patients with PM/DM, the anti-MDA5 antibody measurements obtained from the ELISA and IP assay were highly concordant; the ELISA exhibited an analytical sensitivity of 98.2%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.5% (compared to the IP assay). Anti-MDA5 antibodies were detected in 22.7% of the DM patients, but not in any of the patients with PM, non-PM/DM CTD, or IIP. Clinically amyopathic DM, RP-ILD, arthritis, and fever were more prevalent in DM patients who were anti-MDA5 antibody-positive than in those who were antibody-negative (P ≤ 0.0002 for all comparisons). In addition, anti-MDA5 antibody-positive patients with RP-ILD exhibited higher antibody levels than those without RP-ILD (P = 0.006).ConclusionOur newly developed ELISA can detect anti-MDA5 antibodies as efficiently as the gold standard IP assay and has the potential to facilitate the routine clinical measurement of anti-MDA5 antibodies in patients who suspected to have DM. 相似文献
75.
Kana Hasegawa Satomi Tanaka Fumihiro Fujiki Soyoko Morimoto Katsuhiko Nakano Hiroko Kinoshita Atsushi Okumura Yuka Fujioka Rika Urakawa Hiroko Nakajima Naoya Tatsumi Jun Nakata Satoshi Takashima Sumiyuki Nishida Akihiro Tsuboi Yoshihiro Oka Yusuke Oji Eiji Miyoshi Takako Hirata Atsushi Kumanogoh Haruo Sugiyama Naoki Hosen 《PloS one》2016,11(3)
To improve cancer immunotherapy, it is important to understand how tumor cells counteract immune-surveillance. In this study, we sought to identify cell-surface molecules associated with resistance of leukemia cells to cytotoxic T cell (CTL)-mediated cytolysis. To this end, we first established thousands of monoclonal antibodies (mAbs) that react with MLL/AF9 mouse leukemia cells. Only two of these mAbs, designated R54 and B2, bound preferentially to leukemia cells resistant to cytolysis by a tumor cell antigen–specific CTLs. The antigens recognized by these mAbs were identified by expression cloning as the same protein, CD43, although their binding patterns to subsets of hematopoietic cells differed significantly from each other and from a pre-existing pan-CD43 mAb, S11. The epitopes of R54 and B2, but not S11, were sialidase-sensitive and expressed at various levels on leukemia cells, suggesting that binding of R54 or B2 is associated with the glycosylation status of CD43. R54high leukemia cells, which are likely to express sialic acid-rich CD43, were highly resistant to CTL-mediated cytolysis. In addition, loss of CD43 in leukemia cells or neuraminidase treatment of leukemia cells sensitized leukemia cells to CTL-mediated cell lysis. These results suggest that sialic acid-rich CD43, which harbors multiple sialic acid residues that impart a net negative surface charge, protects leukemia cells from CTL-mediated cell lysis. Furthermore, R54high or B2high leukemia cells preferentially survived in vivo in the presence of adaptive immunity. Taken together, these results suggest that the glycosylation status of CD43 on leukemia is associated with sensitivity to CTL-mediated cytolysis in vitro and in vivo. Thus, regulation of CD43 glycosylation is a potential strategy for enhancing CTL-mediated immunotherapy. 相似文献
76.
Yamanaka Akihiro Beuckmann Carsten T. Willie Jon T. Hara Junko Tsujino Natsuko Goto Katsutoshi Yanagisawa Masashi Sakurai Takeshi 《Sleep and biological rhythms》2016,2(1):S57-S57
Sleep and Biological Rhythms - 相似文献
77.
Akihiro Ohyama Junko Toyomura Toshiaki Tachibana Seiji Isonishi Haruka Takahashi Hiroshi Ishikawa 《Human cell》2016,29(4):188-196
A cell line, designated NOCC, was established from the ascites of a patient with clear cell adenocarcinoma of the ovary. The cell line has been grown without interruption and continuously propagated by serial passaging (more than 76 times) over 7 years. The cells are spherical to polygonal-shaped, display neoplastic, and pleomorphic features, and grow in a jigsaw puzzle-like pattern while forming monolayers without contact inhibition. The cells proliferate rapidly, but are easily floated as a cell sheet. The population doubling time is about 29 h. The number of chromosomes ranges from 60 to 83. The modal number of chromosomes is 70–74 at the 30th passage. NOCC cells secreted 750.5 ng/ml of VEGF over 3 days of culture. Hypoxia inducible factor-1α (HIF-1α) is a primary regulator of VEGF under hypoxic conditions. NOCC cells were not sensitive to the anticancer drugs BEV, DOX, GEM, ETP, CDDP, or TXT. The graft of NOCC cells to a scid mouse displayed similar histological aspects to the original tumor. Both the NOCC cells and the graft of the NOCC cells gave a positive PAS reaction. 相似文献
78.
Naohiro Yoshida Jin Endo Kenichiro Kinouchi Hiroki Kitakata Hidenori Moriyama Masaharu Kataoka Tsunehisa Yamamoto Kohsuke Shirakawa Satoshi Morimoto Akira Nishiyama Akihiro Hashiguchi Itsuro Higuchi Keiichi Fukuda Atsuhiro Ichihara Motoaki Sano 《Aging cell》2019,18(5)
To extend life expectancy and ensure healthy aging, it is crucial to prevent and minimize age‐induced skeletal muscle atrophy, also known as sarcopenia. However, the disease's molecular mechanism remains unclear. The age‐related Wnt/β‐catenin signaling pathway has been recently shown to be activated by the (pro)renin receptor ((P)RR). We report here that (P)RR expression was increased in the atrophied skeletal muscles of aged mice and humans. Therefore, we developed a gain‐of‐function model of age‐related sarcopenia via transgenic expression of (P)RR under control of the CAG promoter. Consistent with our hypothesis, (P)RR‐Tg mice died early and exhibited muscle atrophy with histological features of sarcopenia. Moreover, Wnt/β‐catenin signaling was activated and the regenerative capacity of muscle progenitor cells after cardiotoxin injury was impaired due to cell fusion failure in (P)RR‐Tg mice. In vitro forced expression of (P)RR protein in C2C12 myoblast cells suppressed myotube formation by activating Wnt/β‐catenin signaling. Administration of Dickkopf‐related protein 1, an inhibitor of Wnt/β‐catenin signaling, and anti‐(P)RR neutralizing antibody, which inhibits binding of (P)RR to the Wnt receptor, significantly improved sarcopenia in (P)RR‐Tg mice. Furthermore, the use of anti‐(P)RR neutralizing antibodies significantly improved the regenerative ability of skeletal muscle in aged mice. Finally, we show that Yes‐associated protein (YAP) signaling, which is coordinately regulated by Wnt/β‐catenin, contributed to the development of (P)RR‐induced sarcopenia. The present study demonstrates the use of (P)RR‐Tg mice as a novel sarcopenia model, and shows that (P)RR‐Wnt‐YAP signaling plays a pivotal role in the pathogenesis of this disease. 相似文献
79.
Takashi Yazawa Yoshitaka Imamichi Koh‐ichi Yuhki Junsuke Uwada Daisuke Mikami Masayuki Shimada Kaoru Miyamoto Takeshi Kitano Satoru Takahashi Toshio Sekiguchi Nobuo Suzuki Md. Rafiqul Islam Khan Fumitaka Ushikubi Akihiro Umezawa Takanobu Taniguchi 《Molecular reproduction and development》2019,86(7):786-797
80.
Chemical syntheses of complex-type glycans derived from the eggs of parasitic helminths, Schistosoma mansoni and Schistosoma japonicum were achieved. In addition, their analogs, which lack xylose and/or fucose residue(s), are described. These branched sugar chains were synthesized regio- and stereoselectively by using beta-mannosylation, desilylation under high-pressure and glycosylation in frozen solvent as key transformations. 相似文献