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901.
Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling 总被引:2,自引:0,他引:2
Maeder CI Hink MA Kinkhabwala A Mayr R Bastiaens PI Knop M 《Nature cell biology》2007,9(11):1319-1326
Signal transduction through mitogen-activated protein kinase (MAPK) cascades is thought to occur through the assembly of macromolecular complexes. We quantified the abundance of complexes in the cytoplasm among the MAPKs Ste11, Ste7, Fus3 and the scaffold protein Ste5 in yeast pheromone signalling using fluorescence cross-correlation spectroscopy (FCCS). Significant complex concentrations were observed that remained unchanged on pheromone stimulation, demonstrating that global changes in complex abundances do not contribute to the transmission of signal through the cytoplasm. On the other hand, investigation of the distribution of active Fus3 (Fus3(PP)) across the cytoplasm using fluorescence lifetime imaging microscopy (FLIM) revealed a gradient of Fus3(PP) activity emanating from the tip of the mating projection. Spatial partitioning of Fus3 activating kinases to this site and deactivating phosphatases in the cytoplasm maintain this Fus3(PP)-activity distribution. Propagation of signalling from the shmoo is, therefore, spatially constrained by a gradient-generating reaction-diffusion mechanism. 相似文献
902.
The aim of this study was to investigate the nature of Supercell coating, an on-line tablet coater that employed a unique
pattern of airflow. Tablets coated at different spray rates (4, 6, 8, 10, and 12 mL/min) were analyzed to investigate the
influence of different wetting conditions on the quality of coats formed. Scanning electron micrographs showed that tablet
coats formed at a spray rate of 4 mL/min consisted of spray-dried droplets that did not coalesce. At a spray rate of 6 mL/min,
surface roughness was found to be lower than at the other spray rates, and the coat appeared smoothest, whereby droplets seemed
fused together. At higher spray rates, the droplets appeared as branching arms and scale-like structures. This was attributed
to the spread of spray droplets by the processing air and mass transfer of wet coating materials between tablets. Further
tests showed that coats formed at higher spray rates had higher drug yield, drug uniformity, color uniformity, and density.
However, the variability in coat thickness was increased due to the mass transfer of coats and dissolution of tablet core
surfaces by the coating material. Since coats of different characteristics can be formed in Supercell coating, the choice
of wetting conditions would depend on the type of coat required and the coating materials used.
Published: August 10, 2007 相似文献
903.
904.
Prashanthi Ramesh Tamsin R. M. Lannagan Rene Jackstadt Lidia Atencia Taboada Nico Lansu Pratyaksha Wirapati Sander R. van Hooff Danielle Dekker Jessica Pritchard Aleksandar B. Kirov Sanne M. van Neerven Sabine Tejpar Geert J. P. L. Kops Owen J. Sansom Jan Paul Medema 《Cell death and differentiation》2021,28(12):3282
Evasion of apoptosis is a hallmark of cancer, which is frequently mediated by upregulation of the antiapoptotic BCL-2 family proteins. In colorectal cancer (CRC), previous work has highlighted differential antiapoptotic protein dependencies determined by the stage of the disease. While intestinal stem cells (ISCs) require BCL-2 for adenoma outgrowth and survival during transformation, ISC-specific MCL1 deletion results in disturbed intestinal homeostasis, eventually contributing to tumorigenesis. Colon cancer stem cells (CSCs), however, no longer require BCL-2 and depend mainly on BCL-XL for their survival. We therefore hypothesized that a shift in antiapoptotic protein reliance occurs in ISCs as the disease progresses from normal to adenoma to carcinoma. By targeting antiapoptotic proteins with specific BH3 mimetics in organoid models of CRC progression, we found that BCL-2 is essential only during ISC transformation while MCL1 inhibition did not affect adenoma outgrowth. BCL-XL, on the other hand, was crucial for stem cell survival throughout the adenoma-to-carcinoma sequence. Furthermore, we identified that the limited window of BCL-2 reliance is a result of its downregulation by miR-17-5p, a microRNA that is upregulated upon APC-mutation driven transformation. Here we show that BCL-XL inhibition effectively impairs adenoma outgrowth in vivo and enhances the efficacy of chemotherapy. In line with this dependency, expression of BCL-XL, but not BCL-2 or MCL1, directly correlated to the outcome of chemotherapy-treated CRC patients. Our results provide insights to enable the rational use of BH3 mimetics in CRC management, particularly underlining the therapeutic potential of BCL-XL targeting mimetics in both early and late-stage disease.Subject terms: Cancer models, Cancer stem cells, Cell biology 相似文献
905.
Katelyn M. Gostic Lauren McGough Edward B. Baskerville Sam Abbott Keya Joshi Christine Tedijanto Rebecca Kahn Rene Niehus James A. Hay Pablo M. De Salazar Joel Hellewell Sophie Meakin James D. Munday Nikos I. Bosse Katharine Sherrat Robin N. Thompson Laura F. White Jana S. Huisman Jrmie Scire Sebastian Bonhoeffer Tanja Stadler Jacco Wallinga Sebastian Funk Marc Lipsitch Sarah Cobey 《PLoS computational biology》2021,17(12)
906.
Mechanical forces play pivotal roles in regulating cell shape, function, and fate. Key players that govern the mechanobiological interplay are the mechanosensitive proteins found on cell membranes and in cytoskeleton. Their unique nanomechanics can be interrogated using single-molecule tweezers, which can apply controlled forces to the proteins and simultaneously measure the ensuing structural changes. Breakthroughs in high-resolution tweezers have enabled the routine monitoring of nanometer-scale, millisecond dynamics as a function of force. Undoubtedly, the advancement of structural biology will be further fueled by integrating static atomic-resolution structures and their dynamic changes and interactions observed with the force application techniques. In this minireview, we will introduce the general principles of single-molecule tweezers and their recent applications to the studies of force-bearing proteins, including the synaptic proteins that need to be categorized as mechanosensitive in a broad sense. We anticipate that the impact of nano-precision approaches in mechanobiology research will continue to grow in the future. 相似文献
907.
Nuno Maia Sven Potelle Hamide Yildirim Sandrine Duvet Shyam K. Akula Celine Schulz Elsa Wiame Alexander Gheldof Katherine OKane Abbe Lai Karen Sermon Maïa Proisy Philippe Loget Tania Atti-Bitach Chlo Quelin Ana Maria Fortuna Ana Rita Soares Arjan P.M. de Brouwer Emile Van Schaftingen Marie-Ccile Nassogne Christopher A. Walsh Katrien Stouffs Paula Jorge Anna C. Jansen Franois Foulquier 《American journal of human genetics》2022,109(2):345-360
908.
Activated satellite cells fail to restore myonuclear number in spinal cord transected and exercised rats 总被引:2,自引:0,他引:2
Dupont-Versteegden Esther E.; Murphy Rene J. L.; Houle John D.; Gurley Cathy M.; Peterson Charlotte A. 《American journal of physiology. Cell physiology》1999,277(3):C589
In this study, possible mechanisms underlying soleus muscleatrophy after spinal cord transection and attenuation of atrophy withcycling exercise were studied. Adult female Sprague-Dawley rats weredivided into three groups; in two groups the spinal cord was transectedby a lesion at T10. One group wastransected and killed 10 days later, and another group was transectedand exercised for 5 days starting 5 days after transection. The third group served as an uninjured control. All animals received acontinuous-release 5'-bromo-2'-deoxyuridine pellet 10 daysbefore they were killed. Transection alone and transection withexercise lead to activation of satellite cells, but only the exercisegroup showed a trend toward an increase in the number of proliferatingsatellite cells. In all cases the number of activated satellite cellswas significantly higher than the number that divided. Although thenumber of cells undergoing proliferation increased with exercise, noincrease in fusion of satellite cells into muscle fibers was apparent. Spinal cord transection resulted in a 25% decrease in myonuclear number, and exercise was not associated with a restoration of myonuclear number. The number of apoptotic nuclei was increased aftertransection, and exercise attenuated this increase. However, thedecrease in apoptotic nuclei with exercise did not significantly affectmyonuclear number. We conclude that apoptotic nuclear loss likelycontributes to loss of nuclei during muscle atrophy associated withspinal cord transection and that exercise can maintain muscle mass, atleast in the short term, without restoration of myonuclear number. 相似文献
909.
Henar Alonso-Pimentel Hayward G. Spangler Rene Rogers Daniel R. Papaj 《Journal of Insect Behavior》2000,13(4):511-524
Courtship signaling via wing vibration, accompanied by sound production, has been reported in several species of tephritids. In this large family of flies, sound communication as well as complex courtship displays appears to be restricted to species with lekking mating systems (i.e., Mediterranean fruit fly, Anastrepha and Dacus species). In contrast, in tephritid species with resource-defense mating systems, such as species in the genus Rhagoletis, little or no courtship behavior, acoustical or otherwise, has been described. Wing displays in Rhagoletis species have been considered to play a visual role. This study describes a distinctive wing display performed by males of the walnut fly, Rhagoletis juglandis. Laboratory experiments and field observations demonstrate that the male wing display plays a role in courtship. We used sound and vibration detectors to record the signals produced by this wing display. Using a combination of techniques, we were able to record both the very low-frequency vibration and its accompanying airborne infrasound (12–22 Hz) produced by the males. 相似文献