全文获取类型
收费全文 | 1162篇 |
免费 | 84篇 |
国内免费 | 1篇 |
专业分类
1247篇 |
出版年
2022年 | 10篇 |
2021年 | 16篇 |
2020年 | 13篇 |
2019年 | 7篇 |
2018年 | 15篇 |
2017年 | 21篇 |
2016年 | 23篇 |
2015年 | 44篇 |
2014年 | 53篇 |
2013年 | 66篇 |
2012年 | 75篇 |
2011年 | 71篇 |
2010年 | 40篇 |
2009年 | 45篇 |
2008年 | 69篇 |
2007年 | 46篇 |
2006年 | 60篇 |
2005年 | 45篇 |
2004年 | 48篇 |
2003年 | 52篇 |
2002年 | 50篇 |
2001年 | 42篇 |
2000年 | 47篇 |
1999年 | 39篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 11篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 10篇 |
1992年 | 19篇 |
1991年 | 23篇 |
1990年 | 16篇 |
1989年 | 16篇 |
1988年 | 9篇 |
1987年 | 11篇 |
1986年 | 16篇 |
1985年 | 11篇 |
1983年 | 9篇 |
1982年 | 6篇 |
1980年 | 4篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 6篇 |
1972年 | 3篇 |
1970年 | 9篇 |
排序方式: 共有1247条查询结果,搜索用时 0 毫秒
121.
Toshio Yoshida Akira Komatsu Motoichi Indo 《Bioscience, biotechnology, and biochemistry》2013,77(6):433-437
Menthols were converted to Δ3-menthone enol acetate (VII) via menthones having only one asymmetric carbon atom. It was shown that the optical rotation of menthone enol acetate was proportional to the optical purity of starting menthols. Optical purity of original menthol could, therefore, be determined by optical rotation of menthone enol acetate derived from. 相似文献
122.
A Matsuda H Sugiura K Matsuyama H Matsumoto S Ichikawa K Komatsu 《Biochemical and biophysical research communications》1992,182(3):995-1001
Acetyl CoA: deacetylcephalosporin C o-acetyltransferase(DCPC-ATF) catalyses the final step in the biosynthesis of cephalosporin C, the conversion of deacetylcephalosporin C to cephalosporin C. A cDNA encoding DCPC-ATF has been isolated from a cDNA library of a cephalosporin C producing fungus Acremonium chrysogenum using oligonucleotide probes based on N-terminal amino acid sequences of the enzyme. The cDNA contains a single large open reading frame for a putative precursor consisting of 12 amino acid(AA) leader peptide of unknown function, 274 AA large subunit and 126 AA small subunit at the carboxyl end. The cDNA was expressed in yeast exhibiting a functional DCPC-ATF activity. It was also indicated that the leader peptide was not essential for expression of the enzyme activity. The primary structure of DCPC-ATF shows significant homology with those of acetyl CoA: homoserine o-acetyltransferase in Saccharomyces cerevisiae and Ascobolas immersus. 相似文献
123.
Ichimura Y Kumanomidou T Sou YS Mizushima T Ezaki J Ueno T Kominami E Yamane T Tanaka K Komatsu M 《The Journal of biological chemistry》2008,283(33):22847-22857
Impairment of autophagic degradation of the ubiquitin- and LC3-binding protein "p62" leads to the formation of cytoplasmic inclusion bodies. However, little is known about the sorting mechanism of p62 to autophagic degradation. Here we identified a motif of murine p62 consisting of 11 amino acids (Ser334-Ser344) containing conserved acidic and hydrophobic residues across species, as an LC3 recognition sequence (LRS). The crystal structure of the LC3-LRS complex at 1.56 angstroms resolution revealed interaction of Trp340 and Leu343 of p62 with different hydrophobic pockets on the ubiquitin fold of LC3. In vivo analyses demonstrated that p62 mutants lacking LC3 binding ability accumulated without entrapping into autophagosomes in the cytoplasm and subsequently formed ubiquitin-positive inclusion bodies as in autophagy-deficient cells. These results demonstrate that the intracellular level of p62 is tightly regulated by autophagy through the direct interaction of LC3 with p62 and reveal that selective turnover of p62 via autophagy controls inclusion body formation. 相似文献
124.
Numerous tools for Zn2+ sensing in living cells have become available in the past three years. Among them, fluorescence imaging using fluorescent sensor molecules has been the most popular approach. Some of these sensor molecules can be used to visualize Zn2+ in living cells. Some of the biological functions of Zn2+ have been clarified using these sensor molecules, especially in neuronal cells, which contain a high concentration of free Zn2+. 相似文献
125.
Cold stress changes the concanavalin A-positive glycosylation pattern of proteins expressed in the basal parts of rice leaf sheaths 总被引:3,自引:0,他引:3
Post-translational modifications such as glycosylation are important for changing the properties and functions of proteins.
To analyze the importance of glycosylation during cold stress in rice, a proteomics approach was used. Proteins extracted
from the basal part of rice leaf sheaths were separated by two-dimensional polyacrylamide gel electrophoresis, and subjected
to lectin blot analysis using concanavalin A. From a total of 250 detected proteins, 22 reacted with the lectin, suggesting
that they were N-glycosylated proteins. To determine how N-glycosylation of these proteins is affected by cold stress, rice seedlings were incubated at 5°C for 48 h, and proteins extracted
from the basal parts of leaf sheaths were analyzed by the lectin blot assay. Cold stress changed the reactivity toward the
lectin for 12 of the 22 glycoproteins. The identity of the 12 proteins was determined by protein sequencing and mass spectrometry
with the majority of these glycoproteins being categorized as involved in energy production. Furthermore, calreticulin, one
of the 12 glycoproteins, was also phosphorylated as a result of cold stress. These results indicate that cold stress of the
basal parts of rice leaf sheaths changes the glycosylation and phosphorylation profiles of calreticulin, a key protein that
regulates the quality control of other proteins. 相似文献
126.
Komatsu H Awano H Tanikawa H Itou K Ikeda I 《Nucleosides, nucleotides & nucleic acids》2001,20(4-7):1291-1293
A chemical synthesis of 2-deoxyribose-1-phosphate 2 and its enzymatic conversion into purine 2'-deoxynucleosides (dNus) are shown. Besides the chemo-enzymatic process for purine dNus, a modified process for practical dC preparation is also established. Consequently, a series of practical manufacturing processes of all four dNus have been realized via novel strategies. 相似文献
127.
Definition of sequence requirements for latency-associated nuclear antigen 1 binding to Kaposi's sarcoma-associated herpesvirus DNA 下载免费PDF全文
In latent infection, Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen 1 (LANA1)-specific binding to KSHV terminal repeat DNA mediates multicopy episome persistence. We now use electrophoretic mobility shift assays to investigate LANA1 binding to its 20-bp cognate sequence. Mutations at positions 6, 7, and 8 ((6)CCC(8)) severely reduced LANA1 binding, whereas mutations at other positions only modestly reduced binding. Since (6)CCC(8) is in the 5' half of an inverted repeat sequence, these results are consistent with an asymmetric role for the inverted repeat in LANA1 binding. 相似文献
128.
Takashi Hattori Takashi Mine Nobukazu Komatsu Akira Yamada Kyogo Itoh Hitoshi Shiozaki Kiyotaka Okuno 《Cancer immunology, immunotherapy : CII》2009,58(11):1843-1852
To investigate the safety and immunological responses of personalized peptide vaccination in combination with oral administration
of UFT and UZEL for metastatic colorectal carcinoma (mCRC), fourteen patients were enrolled in the present study. Peptides
were determined based on the presence of peptide-specific cytotoxic T lymphocyte precursors and IgG in each patient. A maximum
of four peptides were subcutaneously administered weekly with UFT (300 mg/m2 day−1) and UZEL (75 mg/day) for 4 weeks, followed by 1 week of rest. This therapy was well-tolerated although there was a grade-3
skin reaction at the vaccination site in one patient. An increase in peptide-specific interferon-γ production or peptide-specific
IgG after the tenth vaccination was observed in nine of ten or eight of ten patients tested, respectively. IgG responses were
well correlated with overall survival (P = 0.0215). The safety and immunological responsiveness of the present therapy suggest that this combination would be of clinical
benefit for mCRC patients, and further trials are merited.
T. Hattori and T. Mine equally contributed to this work. 相似文献
129.
Yoshitaka Sunami Marito Araki Yumi Hironaka Soji Morishita Masaki Kobayashi Ei Leen Liew Yoko Edahiro Miyuki Tsutsui Akimichi Ohsaka Norio Komatsu 《PloS one》2013,8(2)
Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular differentiation in leukemic cells. The sirtuin inhibitors tenovin-6 and BML-266 induce granulocytic differentiation in the acute promyelocytic leukemia (APL) cell line NB4. This differentiation is likely caused by an inhibition of SIRT2 deacetylase activity, judging from the accumulation of acetylated α-tubulin, a major SIRT2 substrate. Unlike the clinically used differentiation inducer all-trans retinoic acid, tenovin-6 shows limited effects on promyelocytic leukemia–retinoic acid receptor α (PML-RAR-α) stability and promyelocytic leukemia nuclear body formation in NB4 cells, suggesting that tenovin-6 does not directly target PML-RAR-α activity. In agreement with this, tenovin-6 induces cellular differentiation in the non-APL cell line HL-60, where PML-RAR-α does not exist. Knocking down SIRT2 by shRNA induces granulocytic differentiation in NB4 cells, which demonstrates that the inhibition of SIRT2 activity is sufficient to induce cell differentiation in NB4 cells. The overexpression of SIRT2 in NB4 cells decreases the level of granulocytic differentiation induced by tenovin-6, which indicates that tenovin-6 induces granulocytic differentiation by inhibiting SIRT2 activity. Taken together, our data suggest that targeting SIRT2 is a viable strategy to induce leukemic cell differentiation. 相似文献
130.
Watanobe T Okumura N Ishiguro N Nakano M Matsui A Sahara M Komatsu M 《Molecular ecology》1999,8(9):1509-1512
Mitochondrial genetic variations were used to investigate the relationships between two Japanese wild boars, Japanese wild boar (Sus scrofa leucomystax) and Ryukyu wild boar (S.s. riukiuanus). Nucleotide sequences of the control (27 haplotypes) and cytochrome b (cyt-b) regions (19 haplotypes) were determined from 59 Japanese wild boars, 13 Ryukyu wild boars and 22 other boars and pigs. From phylogenetic analyses, the mtDNA of Ryukyu wild boar has a distinct lineage from that of Japanese wild boar, which was classified into the Asian pig lineage. This result suggests that the Ryukyu wild boar has a separate origin from the Japanese wild boar. 相似文献