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121.
122.
Kurata H Kusumi K Otsuki K Suzuki R Kurono M Tokuda N Takada Y Shioya H Mizuno H Komiya T Ono T Hagiya H Minami M Nakade S Habashita H 《Bioorganic & medicinal chemistry letters》2012,22(1):144-148
Structure-activity relationship (SAR) of sphingosine-1-phosphate receptor agonists with a dihydronaphthalene scaffold was investigated. Compound 1 was modified to improve S1P(1) agonistic activity and in vivo peripheral lymphocyte lowering (PLL) activity without impairing selectivity over S1P(3) agonistic activity. A detailed SAR study of the terminal lipophilic part revealed that the introduction of substituents on the propylene linker and the terminal benzene ring influences in vitro and PLL activities. Compound 6n bearing a (S)-methyl group at the 2-position on the propylene linker and chlorine at the para-position on the terminal benzene ring showed potent hS1P(1) agonistic activity with excellent selectivity over hS1P(3) and in vivo PLL activity in mice. 相似文献
123.
Afendi FM Okada T Yamazaki M Hirai-Morita A Nakamura Y Nakamura K Ikeda S Takahashi H Altaf-Ul-Amin M Darusman LK Saito K Kanaya S 《Plant & cell physiology》2012,53(2):e1
A database (DB) describing the relationships between species and their metabolites would be useful for metabolomics research, because it targets systematic analysis of enormous numbers of organic compounds with known or unknown structures in metabolomics. We constructed an extensive species-metabolite DB for plants, the KNApSAcK Core DB, which contains 101,500 species-metabolite relationships encompassing 20,741 species and 50,048 metabolites. We also developed a search engine within the KNApSAcK Core DB for use in metabolomics research, making it possible to search for metabolites based on an accurate mass, molecular formula, metabolite name or mass spectra in several ionization modes. We also have developed databases for retrieving metabolites related to plants used for a range of purposes. In our multifaceted plant usage DB, medicinal/edible plants are related to the geographic zones (GZs) where the plants are used, their biological activities, and formulae of Japanese and Indonesian traditional medicines (Kampo and Jamu, respectively). These data are connected to the species-metabolites relationship DB within the KNApSAcK Core DB, keyed via the species names. All databases can be accessed via the website http://kanaya.naist.jp/KNApSAcK_Family/. KNApSAcK WorldMap DB comprises 41,548 GZ-plant pair entries, including 222 GZs and 15,240 medicinal/edible plants. The KAMPO DB consists of 336 formulae encompassing 278 medicinal plants; the JAMU DB consists of 5,310 formulae encompassing 550 medicinal plants. The Biological Activity DB consists of 2,418 biological activities and 33,706 pairwise relationships between medicinal plants and their biological activities. Current statistics of the binary relationships between individual databases were characterized by the degree distribution analysis, leading to a prediction of at least 1,060,000 metabolites within all plants. In the future, the study of metabolomics will need to take this huge number of metabolites into consideration. 相似文献
124.
The neural representation of motion aftereffects induced by various visual flows (translational, rotational, motion-in-depth,
and translational transparent flows) was studied under the hypothesis that the imbalances in discharge activities would occur
in favor in the direction opposite to the adapting stimulation in the monkey MST cells (cells in the medial superior temporal
area) which can discriminate the mode (i.e., translational, rotational, or motion-in-depth) of the given flow. In single-unit
recording experiments conducted on anaesthetized monkeys, we found that the rate of spontaneous discharge and the sensitivity
to a test stimulus moving in the preferred direction decreased after receiving an adapting stimulation moving in the preferred
direction, whereas they increased after receiving an adapting stimulation moving in the null direction. To consistently explain
the bidirectional perception of a transparent visual flow and its unidirectional motion aftereffect by the same hypothesis,
we need to assume the existence of two subtypes of MST D cells which show directionally selective responses to a translational
flow: component cells and integration cells. Our physiological investigation revealed that the MST D cells could be divided
into two types: one responded to a transparent flow by two peaks at the instances when the direction of one of the component
flow matched the preferred direction of the cell, and the other responded by a single peak at the instance when the direction
of the integrated motion matched the preferred direction. In psychophysical experiments on human subjects, we found evidence
for the existence of component and integration representations in the human brain. To explain the different motion perceptions,
i.e., two transparent flows during presentation of the flows and a single flow in the opposite direction to the integrated
flows after stopping the flow stimuli, we suggest that the pattern-discrimination system can select the motion representation
that is consistent with the perception of the pattern from two motion representations. We discuss the computational aspects
related to the integration of component motion fields. 相似文献
125.
Kinya Katayama Masako Miyoshi Kensuke Nabeta Hiroyuki Tazaki 《Phytochemistry letters》2012,5(4):761-765
The in vitro cultured liverwort Jungermannia subulata produces the unique molecule subulatin. In this study, we examined the incorporation of [1-13C] and [1,2-13C2] glucose, [2-13C] arabinose, [2-13C] caffeic acid, and [1-13C] phenylalanine into subulatin. The trilobatinoic acid C unit of subulatin incorporated 13C atoms from [1-13C] and [1,2-13C2] glucose and from [2-13C] arabinose but not from any other of the other precursors. Based on these results and labeling patterns, the trilobatinoic acid C unit of subulatin appears to be biosynthesized from arabinose-5-phosphate and phosphoenolpyruvate. 相似文献
126.
Yamachika E Tsujigiwa H Matsubara M Hirata Y Kita K Takabatake K Mizukawa N Kaneda Y Nagatsuka H Iida S 《Journal of molecular histology》2012,43(2):223-233
Some progress has been made in development of methods to regenerate bone from cultured cells, however no method is put to
practical use. Here, we developed methods to isolate, purify, and expand mesenchymal stem cells (MSCs) from mouse compact
bone that may be used to regenerate bone in vivo. These cells were maintained in long-term culture and were capable of differentiating
along multiple lineages, including chondrocyte, osteocyte, and adipocyte trajectories. We used standard cell isolation and
culture methods to establish cell cultures from mouse compact bone and bone marrow. Cultures were grown in four distinct media
to determine the optimal composition of culture medium for bone-derived MSCs. Putative MSCs were subjected to flow cytometry,
alkaline phosphatase assays, immunohistochemical staining, and several differentiation assays to assess cell identity, protein
expression, and developmental potential. Finally, we used an in vivo bone formation assay to determine whether putative MSCs
were capable of regenerating bone. We found that compact bone of mice was a better source of MCSs than the bone marrow, that
growth in plastic flasks served to purify MSCs from hematopoietic cells, and that MSCs grown in basic fibroblast growth factor
(bFGF)-conditioned medium were, based on multiple criteria, superior to those grown in leukemia inhibitory factor-conditioned
medium. Moreover, we found that the MSCs isolated from compact bone and grown in bFGF-conditioned medium were capable of supporting
bone formation in vivo. The methods and results described here have implications for understanding MSC biology and for clinical
purpose. 相似文献
127.
Eguchi K Manabe I Oishi-Tanaka Y Ohsugi M Kono N Ogata F Yagi N Ohto U Kimoto M Miyake K Tobe K Arai H Kadowaki T Nagai R 《Cell metabolism》2012,15(4):518-533
Highlights? Palmitate induces β cell dysfunction by activating inflammatory processes in islets ? β cells sense palmitate via the TLR4 pathway and recruit M1 macrophages to islets ? M1 macrophages play a pivotal role in palmitate-induced β cell dysfunction ? M1 macrophages and inflammation also play a role in β cell dysfunction in T2D models 相似文献
128.
Minehara H Narita A Naka K Tanaka K Chujo M Nagao M Chujo Y 《Bioorganic & medicinal chemistry》2012,20(15):4675-4679
We report the tumor cell-selective prodrugs based on the arsonic acid-presenting iron oxide nanoparticles. We synthesized the well-dispersed nanoparticles having arsonoacetic acid which is composed of the low toxic As(V) form. From the analyses of the reaction products, it is suggested that the reduction by dithiothreitol with arsonoacetic acid and the modified nanoparticles could generate the highly-toxic As(III) species. In the MTT assays, it was found that the cell viabilities of HeLaS3 and especially HepG2 were reduced in the presence of the modified nanoparticles. In contrast, a slight effect on viability was observed with primary mouse hepatocytes. The viabilities showed good agreements with the amounts of intracellular reduced glutathione concentrations. Furthermore, the valid concentrations of the modified nanoparticles for tumor-specific cytotoxicity were similar level in MRI measurements. These results indicate that arsonic acid-presenting nanoparticles should be a good platform for developing highly-sensitive tumor-specific prodrugs. 相似文献
129.
Rahman Md. Mostafeezur Hossain Md. Zakir Hanako Takatsuji Yoshiaki Yamada Kensuke Yamamura Junichi Kitagawa 《PloS one》2012,7(11)
Cannabinoids have been reported to be involved in affecting various biological functions through binding with cannabinoid receptors type 1 (CB1) and 2 (CB2). The present study was designed to investigate whether swallowing, an essential component of feeding behavior, is modulated after the administration of cannabinoid. The swallowing reflex evoked by the repetitive electrical stimulation of the superior laryngeal nerve in rats was recorded before and after the administration of the cannabinoid receptor agonist, WIN 55-212-2 (WIN), with or without CB1 or CB2 antagonist. The onset latency of the first swallow and the time intervals between swallows were analyzed. The onset latency and the intervals between swallows were shorter after the intravenous administration of WIN, and the strength of effect of WIN was dose-dependent. Although the intravenous administration of CB1 antagonist prior to intravenous administration of WIN blocked the effect of WIN, the administration of CB2 antagonist did not block the effect of WIN. The microinjection of the CB1 receptor antagonist directly into the nucleus tractus solitarius (NTS) prior to intravenous administration of WIN also blocked the effect of WIN. Immunofluorescence histochemistry was conducted to assess the co-localization of CB1 receptor immunoreactivity to glutamic acid decarboxylase 67 (GAD67) or glutamate in the NTS. CB1 receptor was co-localized more with GAD67 than glutamate in the NTS. These findings suggest that cannabinoids facilitate the swallowing reflex via CB1 receptors. Cannabinoids may attenuate the tonic inhibitory effect of GABA (gamma-aminobuteric acid) neurons in the central pattern generator for swallowing. 相似文献
130.
Satoh H Shibahara K Tokunaga T Nishi A Tasaki M Hwang SK Okita TW Kaneko N Fujita N Yoshida M Hosaka Y Sato A Utsumi Y Ohdan T Nakamura Y 《The Plant cell》2008,20(7):1833-1849
Plastidial phosphorylase (Pho1) accounts for approximately 96% of the total phosphorylase activity in developing rice (Oryza sativa) seeds. From mutant stocks induced by N-methyl-N-nitrosourea treatment, we identified plants with mutations in the Pho1 gene that are deficient in Pho1. Strikingly, the size of mature seeds and the starch content in these mutants showed considerable variation, ranging from shrunken to pseudonormal. The loss of Pho1 caused smaller starch granules to accumulate and modified the amylopectin structure. Variation in the morphological and biochemical phenotype of individual seeds was common to all 15 pho1-independent homozygous mutant lines studied, indicating that this phenotype was caused solely by the genetic defect. The phenotype of the pho1 mutation was temperature dependent. While the mutant plants grown at 30 degrees C produced mainly plump seeds at maturity, most of the seeds from plants grown at 20 degrees C were shrunken, with a significant proportion showing severe reduction in starch accumulation. These results strongly suggest that Pho1 plays a crucial role in starch biosynthesis in rice endosperm at low temperatures and that one or more other factors can complement the function of Pho1 at high temperatures. 相似文献