全文获取类型
收费全文 | 1561篇 |
免费 | 124篇 |
国内免费 | 2篇 |
出版年
2021年 | 16篇 |
2020年 | 13篇 |
2019年 | 13篇 |
2018年 | 11篇 |
2017年 | 17篇 |
2016年 | 31篇 |
2015年 | 51篇 |
2014年 | 61篇 |
2013年 | 88篇 |
2012年 | 84篇 |
2011年 | 100篇 |
2010年 | 60篇 |
2009年 | 52篇 |
2008年 | 94篇 |
2007年 | 99篇 |
2006年 | 103篇 |
2005年 | 120篇 |
2004年 | 99篇 |
2003年 | 76篇 |
2002年 | 101篇 |
2001年 | 11篇 |
2000年 | 14篇 |
1999年 | 10篇 |
1998年 | 20篇 |
1997年 | 16篇 |
1996年 | 15篇 |
1995年 | 14篇 |
1994年 | 18篇 |
1993年 | 26篇 |
1992年 | 15篇 |
1991年 | 18篇 |
1990年 | 14篇 |
1989年 | 17篇 |
1988年 | 11篇 |
1987年 | 7篇 |
1986年 | 10篇 |
1985年 | 9篇 |
1984年 | 8篇 |
1983年 | 10篇 |
1982年 | 16篇 |
1981年 | 12篇 |
1980年 | 10篇 |
1979年 | 8篇 |
1978年 | 8篇 |
1977年 | 10篇 |
1976年 | 9篇 |
1975年 | 7篇 |
1974年 | 8篇 |
1973年 | 10篇 |
1971年 | 7篇 |
排序方式: 共有1687条查询结果,搜索用时 15 毫秒
1.
Biochemical Study on the Critical Period for Treatment of the Mottled Brindled Mouse 总被引:2,自引:0,他引:2
Hemizygous mottled brindled mice (Mobr/y mice) were treated by subcutaneous injection of copper and were decapitated on postnatal day 14. Cytochrome c oxidase (COX) activity of the brain mitochondria in the mice given 10 micrograms of copper/g on day 4 or 7 showed significant increases compared with that of untreated Mobr/y animals, and these mice had no neurological symptoms. Mice given 10 micrograms of copper/g on day 12 showed neither increases in COX activity nor clinical improvement. The brain levels of copper, noradrenaline, and dopamine in the mice treated on day 12 were the same as those in animals treated on day 4 or 7. The in vitro activities of dopamine-beta-hydroxylase of the brain were also the same among the treated mice, irrespective of the date of treatment. The results indicate that delays in copper treatment produce irreversible changes in COX activity of the brain and lead to clinical unresponsiveness to treatment. 相似文献
2.
Atsushi Takeda Masatoshi Nakamura Hiroaki Fujii Chihiro Uematsu Tatsuya Minamino Paul A. Adlard Ashley I. Bush Haruna Tamano 《PloS one》2014,9(12)
We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits. 相似文献
3.
Masatoshi Togami Daphne Blazka Jun Hayashi 《In vitro cellular & developmental biology. Plant》1988,24(7):699-704
Summary A serum-free, hormone and attachment factor supplemented culture for rat H4 hepatoma cells was established. In the defined
medium (Dulbecco's Modified Eagle's +Ham's F12+insulin, transferrin, fibronectin liver cell growth factor, and sodium selenite),
H4 cells grew equally well as in 10% fetal bovine serum supplemented medium. H4 cells in either defined or serum-containing
culture conditions produce transferrin but not albumin or alpha-fetoprotein. In this paper we have studied the effect of various
hormones and pressor peptides on the production of angiotensinogen by H4 cells cultured in defined conditions. Only glucocorticoid
hormone had a significant effect on the production of angiotensinogen, whereas other hormones previously reported to exert
their effect on angiotensinogen production had little or no effect.
This work was supported by grant P01 CA37589 from the National Institutes of Health, Bethesda, MD. 相似文献
4.
5.
Masatoshi Kataoka Keizoh Kawamura Tamotsu Kondoh Yoichi Wakano Hiroshi Ishida 《FEMS microbiology letters》1993,107(1):111-114
Abstract A factor showing inhibitory activity against human gingival fibrolasts was extracted from the cytosol fraction of Actinobacillus actinomycetemcomitans Y4. The activity markedly inhibited the proliferation of human gingival fibrolasts, but had no effect on cell viability or gross morphology. No such activity was found in cytosol fractions from either Porphyromonas gingivalis 381 or Escherichia coli HB101. The extract from A. actinomycetemcomitans Y4 was then purified by anion-exchange chromatography, hydroxyapatite chromatography and gel-filtration chromatography to give a single band on SDS-PAGE with an apparent molecular mass of 65 kDa. The purification ratio was 183-fold with a recovery rate of 5% compared with the crude extract (starting material) when the activity was assessed by direct cell counts. 相似文献
6.
Daisuke Takamatsu Rie Arai Tohru Miyoshi-Akiyama Kayo Okumura Masatoshi Okura Teruo Kirikae Atsuko Kojima Makoto Osaki 《Applied and environmental microbiology》2013,79(12):3882-3886
Melissococcus plutonius is a fastidious honeybee pathogen, and the addition of KH2PO4 to culture medium is required for its growth. Using genome sequences and a newly developed vector, we showed that mutations in genes encoding Na+/H+ antiporter and cation-transporting ATPase are involved in the potassium requirement for growth. 相似文献
7.
Summary Statistical properties of the ordinary least-squares (OLS), generalized least-squares (GLS), and minimum-evolution (ME) methods of phylogenetic inference were studied by considering the case of four DNA sequences. Analytical study has shown that all three methods are statistically consistent in the sense that as the number of nucleotides examined (m) increases they tend to choose the true tree as long as the evolutionary distances used are unbiased. When evolutionary distances (dij's) are large and sequences under study are not very long, however, the OLS criterion is often biased and may choose an incorrect tree more often than expected under random choice. It is also shown that the variance-covariance matrix of dij's becomes singular as dij's approach zero and thus the GLS may not be applicable when dij's are small. The ME method suffers from neither of these problems, and the ME criterion is statistically unbiased. Computer simulation has shown that the ME method is more efficient in obtaining the true tree than the OLS and GLS methods and that the OLS is more efficient than the GLS when dij's are small, but otherwise the GLS is more efficient.Offprint requests to: M. Nei 相似文献
8.
Bacterial FtsZ assembles and constricts after chromosomal segregation in the course of cell division. Here we examined the localization of FtsZ in multinucleated swarmer cells of Proteus mirabilis by immunostaining. FtsZ was found to localize to the point of karyomitosis in swarmer cells of P. mirabilis, which is equivalent to filamentous mutants of Escherichia coli defective in the ftsI or ftsQ genes that are involved in later steps of cell division. Thus our findings suggest that the appearance of swarmer cells results from cellular functions immediately after FtsZ assembly. 相似文献
9.
Fine-Scale Genetic Structure and Demographic History in the Miyako Islands of the Ryukyu Archipelago
Masatoshi Matsunami Kae Koganebuchi Minako Imamura Hajime Ishida Ryosuke Kimura Shiro Maeda 《Molecular biology and evolution》2021,38(5):2045
The Ryukyu Archipelago is located in the southwest of the Japanese islands and is composed of dozens of islands, grouped into the Miyako Islands, Yaeyama Islands, and Okinawa Islands. Based on the results of principal component analysis on genome-wide single-nucleotide polymorphisms, genetic differentiation was observed among the island groups of the Ryukyu Archipelago. However, a detailed population structure analysis of the Ryukyu Archipelago has not yet been completed. We obtained genomic DNA samples from 1,240 individuals living in the Miyako Islands, and we genotyped 665,326 single-nucleotide polymorphisms to infer population history within the Miyako Islands, including Miyakojima, Irabu, and Ikema islands. The haplotype-based analysis showed that populations in the Miyako Islands were divided into three subpopulations located on Miyakojima northeast, Miyakojima southwest, and Irabu/Ikema. The results of haplotype sharing and the D statistics analyses showed that the Irabu/Ikema subpopulation received gene flows different from those of the Miyakojima subpopulations, which may be related with the historically attested immigration during the Gusuku period (900 − 500 BP). A coalescent-based demographic inference suggests that the Irabu/Ikema population firstly split away from the ancestral Ryukyu population about 41 generations ago, followed by a split of the Miyako southwest population from the ancestral Ryukyu population (about 16 generations ago), and the differentiation of the ancestral Ryukyu population into two populations (Miyako northeast and Okinawajima populations) about seven generations ago. Such genetic information is useful for explaining the population history of modern Miyako people and must be taken into account when performing disease association studies. 相似文献
10.
HengLiang Wu Le Yu Yujin Tong Aimin Ge Shuehlin Yau Masatoshi Osawa Shen Ye 《生物化学与生物物理学报:生物膜》2013,1828(2):642-651
Atomic force microscopy (AFM) is employed to reveal the morphological changes of the supported phospholipid bilayers hydrolyzed by a phospholipase A2 (PLA2) enzyme in a buffer solution at room temperature. Based on the high catalytic selectivity of PLA2 toward l-enantiomer phospholipids, five kinds of supported bilayers made of l- and d-dipalmitoylphosphatidylcholines (DPPC), including l-DPPC (upper leaflet adjacent to solution)/l-DPPC (bottom leaflet) (or l/l in short), l/d, d/l, d/d, and racemic ld/ld, were prepared on a mica surface in gel-phase, to explicate the kinetics and mechanism of the enzyme-induced hydrolysis reaction in detail. AFM observations for the l/l bilayer show that the hydrolysis rate for l-DPPC is significantly increased by PLA2 and most of the hydrolysis products desorb from substrate surface in 40 min. As d-enantiomers are included in the bilayer, the hydrolysis rate is largely decreased in comparison with the l/l bilayer. The time used to hydrolyze the as-prepared bilayers by PLA2 increases in the sequence of l/l, l/d, ld/ld, and d/l (d/d is inert to the enzyme action). d-enantiomers in the enantiomer hybrid bilayers remain on the mica surface at the end of the hydrolysis reaction. It was confirmed that the hydrolysis reaction catalyzed by PLA2 preferentially occurs at the edges of pits or defects on the bilayer surface. The bilayer structures are preserved during the hydrolysis process. Based on these observations, a novel kinetics model is proposed to quantitatively account for the PLA2-catalyzed hydrolysis of the supported phospholipid bilayers. The model simulation demonstrates that PLA2 mainly binds with lipids at the perimeter of defects in the upper leaflet and leads to a hydrolysis reaction, yielding species soluble to the solution phase. The lipid molecules underneath subsequently flip up to the upper leaflet to maintain the hydrophilicity of the bilayer structure. Our analysis shows that d-enantiomers in the hybrid bilayers considerably reduce the hydrolysis rate by its ineffective binding with PLA2. 相似文献