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111.
Naoki Nishizawa Yoko Kanematsu-Yamaki Masaaki Funata Hiroaki Nagai Ayako Shimizu Hisashi Fujita Junichi Sakamoto Shiro Takekawa Taiji Asami 《Bioorganic & medicinal chemistry letters》2017,27(20):4626-4629
Neuromedin U (NMU) mediates various physiological functions via NMUR1 and NMUR2 receptors. NMUR2 has been considered a promising treatment option for diabetes and obesity. Although NMU-8, a shorter peptide, has potent agonist activity for both receptors, it is metabolically unstable. Therefore, NMU-8 analogs modified with long-chain alkyl moieties via a linker were synthesized. An octadecanoyl analog (17) with amino acid substitutions [αMePhe19, Nle21, and Arg(Me)24] and a linker [Tra-γGlu-PEG(2)] dramatically increased NMUR2 selectivity, with retention of high agonist activity. Subcutaneous administration of 17 induced anorectic activity in C57BL/6J mice. Owing to its high metabolic stability, 17 would be useful in clarifying the physiological role and therapeutic application of NMU. 相似文献
112.
113.
Taiji Kawakatsu Graziana Taramino Jun-Ichi Itoh Justin Allen Yutaka Sato Soon-Kwan Hong Ryan Yule Nobuhiro Nagasawa Mikiko Kojima Makoto Kusaba Hitoshi Sakakibara Hajime Sakai Yasuo Nagato 《The Plant journal : for cell and molecular biology》2009,58(6):1028-1040
Most aerial parts of the plant body are products of the continuous activity of the shoot apical meristem (SAM). Leaves are the major component of the aerial plant body, and their temporal and spatial distribution mainly determines shoot architecture. Here we report the identification of the rice gene PLASTOCHRON3 ( PLA3 )/ GOLIATH ( GO ) that regulates various developmental processes including the rate of leaf initiation (the plastochron). PLA3 / GO encodes a glutamate carboxypeptidase, which is thought to catabolize small acidic peptides and produce small signaling molecules. pla3 exhibits similar phenotypes to pla1 and pla2 – a shortened plastochron, precocious leaf maturation and rachis branch-to-shoot conversion in the reproductive phase. However, in contrast to pla1 and pla2 , pla3 showed pleiotropic phenotypes including enlarged embryo, seed vivipary, defects in SAM maintenance and aberrant leaf morphology. Consistent with these pleiotropic phenotypes, PLA3 is expressed in the whole plant body, and is involved in plant hormone homeostasis. Double mutant analysis revealed that PLA1 , PLA2 and PLA3 are regulated independently but function redundantly. Our results suggest that PLA3 modulates various signaling pathways associated with a number of developmental processes. 相似文献
114.
Specific induction of a 72-kDa heat shock protein protects esophageal mucosa from reflux esophagitis
Yuko Izumi Michiro Otaka Taiji Takahashi Makiko Takada Yuji Shimada Daisuke Asaoka Akihito Nagahara Hideaki Itoh Sumio Watanabe 《Life sciences》2009,84(15-16):517-522
AimsThe aim of this study is to investigate the expression and cytoprotective function of a 72-kDa heat shock protein (HSP72) using a reflux esophagitis model in rats.Main methodsExpression of HSP60, HSP72, and HSP90 in rat esophageal mucosa was evaluated by Western blot analysis before and after hyperthermia (42.5 °C, 20 min). Rats received the operation to produce reflux esophagitis with or without pretreatment with hyperthermia to induce HSPs. The esophageal mucosal damage was evaluated 12 h after the operation.Key findingsExpression of HSP72 was significantly increased by hyperthermia in rat esophageal mucosa. Reflux esophagitis was dramatically prevented when HSP72 was preinduced by hyperthermia. Furthermore, activation of TNF-α and IL-1β in esophageal mucosa was also suppressed.SignificanceThese results suggested that hyperthermia protects the esophageal mucosa in reflux esophagitis model by inducing HSP72 and suppressing proinflammatory cytokine activation. These findings might suggest that HSP-inducing therapy could be a novel and unique therapy for reflux esophagitis. 相似文献
115.
Taiji Adachi Yuki Aonuma Masaki Hojo 《Biochemical and biophysical research communications》2009,389(3):495-500
Bone functional adaptation by remodeling is achieved by harmonized activities of bone cells in which osteocytes in the bone matrix are believed to play critical roles in sensing mechanical stimuli and transmitting signals to osteoclasts/osteoblasts on the bone surface in order to regulate their bone remodeling activities through the lacuno-canalicular network with many slender osteocytic processes. In this study, we investigated the intercellular communication between bone cells, particularly focusing on its directionality, through in vitro observations of the calcium signaling response to mechanical stimulus and its propagation to neighboring cells (NCs). Direct mechanical stimulus was applied to isolated bone cells from chick calvariae, osteocytes (Ocys) and bone surface cells (BSCs) mainly containing osteoblasts, and the percentage of calcium signaling propagation from the stimulated cell to NCs was analyzed. The results revealed that, regardless of the type of stimulated cell, the signaling propagated to BSCs with a significantly higher percentage, implying that calcium signaling propagation between bone cells strongly depends on the type of receiver cell and not the transmitter cell. In addition, in terms of mutual communication between Ocys and BSCs, the percentage of propagation from Ocys to BSCs is significantly higher than that in the opposite direction, suggesting that the calcium signaling mainly propagates asymmetrically with a bias from Ocys in bone matrix to BSCs on bone surfaces. This asymmetric communication between Ocys and BSCs suggests that osteocytic mechanosensing and cellular communications, which significantly affect bone surface remodeling activities to achieve functional adaptation, seem to be well coordinated and active at the location of biologically suitable and mechanically sensitive regions close to the bone surfaces. 相似文献
116.
Tatsuhisa Takahashi Taiji Nagaoka Hirotaka Yanagida Tadashi Saitoh Akira Kamiya Travis Hein Lih Kuo Akitoshi Yoshida 《Journal of Biorheology》2009,23(2):77-86
To quantitatively assess the arteriovenous distribution of hemodynamic parameters throughout the microvascular network of
the human retina, we constructed a retinal microcirculatory model consisting of a dichotomous symmetric branching system.
This system is characterized by a diameter exponent of 2.85, instead of 3 as dictated by Murray’s law, except for the capillary
networks. The value of 2.85 was the sum of a fractal dimension (1.70) and a branch exponent (1.15) of the retinal vasculature.
Following the feeding artery (central retinal artery), each bifurcation was recursively developed at a distance of an individual
branch length [L(r) = 7.4r
1.15] by a centrifugal scheme. The venular tree was formed in the same way. Using this model, we evaluated hemodynamic parameters,
including blood pressure, blood flow, blood velocity, shear rate, and shear stress, within the retinal microcirculatory network
as a function of vessel diameter. The arteriovenous distributions of blood pressure and velocity in the simulation were consistent
with in vivo measurements in the human retina and other vascular beds of small animals. We therefore conclude that the current
theoretical model was useful for quantifying hemodynamics as a function of vessel diameter within the retinal microvascular
network. 相似文献
117.
Tamura H Ishimoto Y Fujikawa T Aoyama H Yoshikawa H Akamatsu M 《Bioorganic & medicinal chemistry》2006,14(21):7160-7174
The androgen receptor (AR) activity of listed chemicals, so called SPEED 98, by the Ministry of the Environment, Japan, and structurally related chemicals was characterized using MDA-kb2 human breast cancer cells stably expressing an androgen-responsive luciferase reporter gene, MMTV-luc. Since our results suggested that chemicals with diverse chemical structures were capable of disrupting the endocrine systems mediated by AR, a comparative molecular field analysis (CoMFA) model was developed to analyze the structural requirements necessary to disrupt AR function. A significant CoMFA model with r(2)=0.825 and q(2)=0.332 was developed for AR antagonist activity of 35 pure antagonists excluding procymidone. On the other hand, a good CoMFA model with r(2)=0.983 and q(2)=0.555 was obtained for antagonist activity of 13 chemicals with both agonist and antagonist activities. The steric and electrostatic properties were sufficient to describe the structural requirements for AR antagonist activity. In addition, the structural difference of AR agonists and antagonists was explained based on CoMFA results and the AR-LBD crystal structure. As several ERalpha agonists such as diethylstilbestrol (DES) acted as AR antagonists, the surface area of the AR ligand-binding domain (LBD) was compared with that of the ERalpha-LBD based on their reported crystal structures to analyze how those ligands interact with LBDs. The surface area of AR-LBD was shown to be smaller than that of ERalpha-LBD and therefore compounds with both estrogenic and antiandrogenic activities can fit well into the ERalpha-LBD but may protrude from the AR-LBD. It is likely that this subtle difference of the surface areas of the LBDs determines whether an ERalpha agonist acts as an AR antagonist or an agonist. 相似文献
118.
Wheelock CE Nakagawa Y Harada T Oikawa N Akamatsu M Smagghe G Stefanou D Iatrou K Swevers L 《Bioorganic & medicinal chemistry》2006,14(4):1143-1159
In this study, 172 diacylhydrazine analogs were examined for their ability to activate an ecdysone (molting hormone)-dependent reporter gene in a silkworm (Bombyx mori) cell-based high-throughput screening assay. The measured EC(50) values (concentration required to cause an effect in 50% of the cells) were used to construct a 3-D QSAR model that describes the ecdysone agonist activities of the diacylhydrazine analogs. Of these compounds, 14 exhibited no activity and were excluded from the 3-D QSAR analysis. The resulting equation described approximately 74% of the activity for 158 compounds. The final equation consisted of 42% electrostatic and 58% steric effects (r(2) = 0.74 and q(2) = 0.45). Comparative molecular field analysis (CoMFA) was used to visualize the steric and electrostatic potential fields that were favorable and unfavorable for biological activity. Of particular interest was the observation that the hydrophobic parameter (logP) was not necessary for describing the observed activities, although previous studies have cited the importance of hydrophobic parameters in both classical and 3-D QSAR analyses of these compounds. Modeling studies of the B. mori ecdysone receptor supported the observed physicochemical parameters required for activity reported by the CoMFA models. Comparison of the present analysis with those performed using other lepidopteran assay systems evidenced a high degree of correlation (r(2) = 0.81 for a Sf-9 cell-based assay and r(2) = 0.89 for a Chilo suppressalis integument-based assay), indicating that it is valid to compare the results generated with the B. mori cell-based system to those generated with previous lepidopteran assays. This novel assay system is amendable to a high-throughput screening format and should greatly increase our ability to discover novel agonists of molting hormone (ecdysone) activity. 相似文献
119.
江西鄱阳湖是长江江豚(Neophocaena phocaenoides)的重要栖息地, 湖中栖息着约400 头江豚。多年的观察表明, 船舶交通是鄱阳湖中江豚面临的重要威胁之一。为了评估船舶通行对长江江豚发声行为的影响,尤其是了解船舶通行期间及其前后江豚的发声和行为特征, 作者于2007 年6 月27 日—7 月1 日在江西鄱阳湖湖口水域采用固定被动声学系统, 即安装在监测点(29°42′38″ N, 116°11′11″ E)的一套水下声学数据记录系统, 对周边通行船舶的水下噪声及江豚声纳信号脉冲事件进行了定点监测和记录, 并对所记录的数据进行了定量和统计分析。在整个监测的109h 中, 声学记录仪共记录到船舶494 艘, 江豚声纳脉冲串信号13413个。船舶出现与江豚出现存在弱的负相关关系(r = -0.029, N = 6550, P Z = -0.370, P> 0.05); 当有船舶经过时, 江豚的发声频次显著降低(Z = -10.050, P Z = -0.275, P> 0.05; Z = -0.119, P> 0.05); 船舶通行之前和之后, 江豚的发声频次、脉冲串持续时间、脉冲间间隔的差异性均不显著(χ2= 5.255, P> 0.05; χ2= 3.511, P> 0.05; χ2= 5.155, P>0.05); 在船舶经过时, 江豚对游动方向没有明显的选择性(χ2= 0.861, P> 0.05)。基于分析结果推测, 在狭窄水域中江豚躲避船舶干扰通常采取“临时性”策略, 而非长距离逃避。由于鄱阳湖湖口水域水道相对狭窄, 尽管研究的结果表明江豚对船舶有一定的敏感反应, 但是在相对狭窄的水域中, 江豚躲避船舶的行为难以充分表现。另外, 江豚对该水域中高密度航行船舶的噪声可能存在一定的“适应性”, 导致当遭遇船舶时, 江豚的声行为反应不十分强烈。因此, 建议有必要在不同尺度的水体中采用声学数据记录仪继续开展类似的观察,以进一步了解江豚对船舶的行为响应, 尤其是观察江豚躲避船舶的行为及发声特征
相似文献
120.
The distribution of contractile forces generated in cytoskeletal stress fibers (SFs) contributes to cellular dynamic functions such as migration and mechanotransduction. Here we describe a novel (to our knowledge) method for measuring local tensions in SFs based on the following procedure: 1), known forces of different magnitudes are applied to an SF in the direction perpendicular to its longitudinal axis; 2), force balance equations are used to calculate the resulting tensions in the SF from changes in the SF angle; and 3), the relationship between tension and applied force thus established is extrapolated to an applied force of zero to determine the preexisting tension in the SF. In this study, we measured tensions in SFs by attaching magnetic particles to them and applying known forces with an electromagnetic needle. Fluorescence microscopy was used to capture images of SFs fluorescently labeled with myosin II antibodies, and analysis of these images allowed the tension in the SFs to be measured. The average tension measured in this study was comparable to previous reports, which indicates that this method may become a powerful tool for elucidating the mechanisms by which cytoskeletal tensions affect cellular functions. 相似文献