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961.
962.
Yasuhito Shirai Takeshi Kouzuki Kenichi Kakefuda Shigeki Moriguchi Atsushi Oyagi Kyoji Horie Shin-ya Morita Masamitsu Shimazawa Kohji Fukunaga Junji Takeda Naoaki Saito Hideaki Hara 《PloS one》2010,5(7)
Background
Diacylglycerol (DG) kinase (DGK) phosphorylates DG to produce phosphatidic acid (PA). Of the 10 subtypes of mammalian DGKs, DGKβ is a membrane-localized subtype and abundantly expressed in the cerebral cortex, hippocampus, and caudate-putamen. However, its physiological roles in neurons and higher brain function have not been elucidated.Methodology/Principal Findings
We, therefore, developed DGKβ KO mice using the Sleeping Beauty transposon system, and found that its long-term potentiation in the hippocampal CA1 region was reduced, causing impairment of cognitive functions including spatial and long-term memories in Y-maze and Morris water-maze tests. The primary cultured hippocampal neurons from KO mice had less branches and spines compared to the wild type. This morphological impairment was rescued by overexpression of DGKβ. In addition, overexpression of DGKβ in SH-SY5Y cells or primary cultured mouse hippocampal neurons resulted in branch- and spine-formation, while a splice variant form of DGKβ, which has kinase activity but loses membrane localization, did not induce branches and spines. In the cells overexpressing DGKβ but not the splice variant form, DGK product, PA, was increased and the substrate, DG, was decreased on the plasma membrane. Importantly, lower spine density and abnormality of PA and DG contents in the CA1 region of the KO mice were confirmed.Conclusions/Significance
These results demonstrate that membrane-localized DGKβ regulates spine formation by regulation of lipids, contributing to the maintenance of neural networks in synaptic transmission of cognitive processes including memory. 相似文献963.
Kosuke Yoshihara Atsushi Tajima Tetsuro Yahata Shoji Kodama Hiroyuki Fujiwara Mitsuaki Suzuki Yoshitaka Onishi Masayuki Hatae Kazunobu Sueyoshi Hisaya Fujiwara Yoshiki Kudo Kohei Kotera Hideaki Masuzaki Hironori Tashiro Hidetaka Katabuchi Ituro Inoue Kenichi Tanaka 《PloS one》2010,5(3)
Background
Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer.Methodology/Principal Findings
Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66–5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20–1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008).Conclusions/Significance
The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer. 相似文献964.
965.
966.
967.
Endo Satoru Takada Masashi Tanaka Hiroki Onizuka Yoshihiko Tanaka Kenichi Miyahara Nobuyuki Baba Hiromi Oishi Ayumu Ishikawa Masayori Hoshi Masaharu Kimura Shinzo Minematsu Masakazu Morimune Yuki Kojima Yasuaki Shizuma Kiyoshi 《Radiation and environmental biophysics》2010,49(3):469-475
Radiation and Environmental Biophysics - This study describes measurements on secondary particles produced by a 290 MeV/n Spread Out Bragg Peak (SOBP) carbon beam. Microdosimetric... 相似文献
968.
969.
Naoko Kida Yousuke Katsuda Yuko Yoshikawa Seiji Komeda Takaji Sato Yoshihiro Saito Masahiko Chikuma Mari Suzuki Tadayuki Imanaka Kenichi Yoshikawa 《Journal of biological inorganic chemistry》2010,15(5):701-707
It is known that a 1,2,3-triazolato-bridged dinuclear platinum(II) complex, [{cis-Pt(NH3)2}2(μ-OH)(μ-1,2,3-ta-N
1,N
2)](NO3)2 (AMTA), shows high in vitro cytotoxicity against several human tumor cell lines and circumvents cross-resistance to cisplatin.
In the present study, we examined a dose- and time-dependent effect of AMTA on the higher-order structure of a large DNA,
T4 phage DNA (166 kbp), by adapting single-molecule observation with fluorescence microscopy. It was found that AMTA induces
the shrinking of DNA into a compact state with a much higher potency than cisplatin. From a quantitative analysis of the Brownian
motion of individual DNA molecules in solution, it became clear that the density of a DNA segment in the compact state is
about 2,000 times greater than that in the absence of AMTA. Circular dichroism spectra suggested that AMTA causes a transition
from the B to the C form in the secondary structure of DNA, which is characterized by fast and slow processes. Electrophoretic
measurements indicated that the binding of AMTA to supercoiled DNA induces unwinding of the double helix. Our results indicate
that AMTA acts on DNA through both electrostatic interaction and coordination binding; the former causes a fast change in
the secondary structure from the B to the C form, whereas the latter promotes shrinking in the higher-order structure as a
relatively slow kinetic process. The shrinking effect of AMTA on DNA is attributable to the possible increase in the number
of bridges along a DNA molecule. It is concluded that AMTA interacts with DNA in a manner markedly different from that of
cisplatin. 相似文献
970.
Yuelong Ma Sangkil Nam Richard Jove Kenichi Yakushijin David A. Horne 《Bioorganic & medicinal chemistry letters》2010,20(1):83-86
A series of ageladine A analogs that include 2-aminoimidazo[4,5-c]azepines (seven-membered rings) and 2-amino-3H-imidazo[4,5-c]pyridine (six-membered rings) derivatives were synthesized and evaluated for their anticancer effects against several human cancer cell lines and MMP-2 inhibition in vitro. Only compounds possessing the aromatic azepine (seven-membered ring) core showed anticancer activity with IC50 values in the low micromolar range. 相似文献