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411.
Aruna Shankaranarayanan Cassandra A. Boguth Susanne Lutz Christiane Vettel Franca Uhlemann Mohamed Aittaleb Thomas Wieland John J.G. Tesmer 《Cellular signalling》2010,22(7):1114-1123
Gαq directly activates p63RhoGEF and closely related catalytic domains found in Trio and Kalirin, thereby linking Gq-coupled receptors to the activation of RhoA. Although the crystal structure of Gαq in complex with the catalytic domains of p63RhoGEF is available, the molecular mechanism of activation has not yet been defined. In this study, we show that membrane translocation does not appear to play a role in Gαq-mediated activation of p63RhoGEF, as it does in some other RhoGEFs. Gαq instead must act allosterically. We next identify specific structural elements in the PH domain that inhibit basal nucleotide exchange activity, and provide evidence that Gαq overcomes this inhibition by altering the conformation of the α6–αN linker that joins the DH and PH domains, a region that forms direct contacts with RhoA. We also identify residues in Gαq that are important for the activation of p63RhoGEF and that contribute to Gα subfamily selectivity, including a critical residue in the Gαq C-terminal helix, and demonstrate the importance of these residues for RhoA activation in living cells. 相似文献
412.
Meka Aruna Theeya Nagaraja Sadaranga Andal Surapaneni Tarakeswari Pisapati V. S. Sirisha Alla G. Reddy Kumarasamy Thangaraj Lalji Singh B. Mohan Reddy 《PloS one》2010,5(1)
Background
We attempt to ascertain if the 3 linked single nucleotide polymorphisms (SNPs) of the Progesterone Receptor (PR) gene (exon 1: G 1031 C; S344T, exon 4: G 1978 T; L660V and exon 5: C 2310 T; H770H) and the PROGINS insertion in the intron G, between exons 7 and 8, are associated with Recurrent Spontaneous Abortion (RSA) in the Indian population.Methodology/Principal Findings
A total of 143 women with RSA and 150 controls were sequenced for all the 8 exons looking for the above 3 linked SNPs of the PR gene earlier implicated in the RSA, as well as for any new SNPs that may be possibly found in the Indian population. PROGINS insertion was screened by electrophoresis. We did not find any new mutations, not observed earlier, in our population. Further, we did not find significant role of the *2 allele (representing the mutant allele at the three SNP loci) or the T2 allele (PROGINS insertion) in the manifestation of RSA. We also did not find an LD pattern between each of the 3 SNPs and the PROGINS insertion.Conclusions/Significance
The results suggest that the PR gene mutations may not play any exclusive role in the manifestation of RSA, and instead, given significantly higher frequency of the *2 allele among the normal women, we surmise if it does not really confer a protective role among the Indian populations, albeit further studies are required in the heterogeneous populations of this region before making any conclusive statement. 相似文献413.
Recent advances in computing technology have enabled microsecond long all-atom molecular dynamics (MD) simulations of biological systems. Methods that can distill the salient features of such large trajectories are now urgently needed. Conventional clustering methods used to analyze MD trajectories suffer from various setbacks, namely (i) they are not data driven, (ii) they are unstable to noise and changes in cut-off parameters such as cluster radius and cluster number, and (iii) they do not reduce the dimensionality of the trajectories, and hence are unsuitable for finding collective coordinates. We advocate the application of principal component analysis (PCA) and a non-metric multidimensional scaling (nMDS) method to reduce MD trajectories and overcome the drawbacks of clustering. To illustrate the superiority of nMDS over other methods in reducing data and reproducing salient features, we analyze three complete villin headpiece folding trajectories. Our analysis suggests that the folding process of the villin headpiece is structurally heterogeneous. 相似文献
414.
415.
Cheng Chen Ramaswamy Krishnan Enhua Zhou Aruna Ramachandran Dhananjay Tambe Kavitha Rajendran Rosalyn M. Adam Linhong Deng Jeffrey J. Fredberg 《PloS one》2010,5(8)
Background
Cells resident in certain hollow organs are subjected routinely to large transient stretches, including every adherent cell resident in lungs, heart, great vessels, gut, and bladder. We have shown recently that in response to a transient stretch the adherent eukaryotic cell promptly fluidizes and then gradually resolidifies, but mechanism is not yet understood.Principal Findings
In the isolated human bladder smooth muscle cell, here we applied a 10% transient stretch while measuring cell traction forces, elastic modulus, F-actin imaging and the F-actin/G-actin ratio. Immediately after a transient stretch, F-actin levels and cell stiffness were lower by about 50%, and traction forces were lower by about 70%, both indicative of prompt fluidization. Within 5min, F-actin levels recovered completely, cell stiffness recovered by about 90%, and traction forces recovered by about 60%, all indicative of resolidification. The extent of the fluidization response was uninfluenced by a variety of signaling inhibitors, and, surprisingly, was localized to the unstretch phase of the stretch-unstretch maneuver in a manner suggestive of cytoskeletal catch bonds. When we applied an “unstretch-restretch” (transient compression), rather than a “stretch-unstretch” (transient stretch), the cell did not fluidize and the actin network did not depolymerize.Conclusions
Taken together, these results implicate extremely rapid actin disassembly in the fluidization response, and slow actin reassembly in the resolidification response. In the bladder smooth muscle cell, the fluidization response to transient stretch occurs not through signaling pathways, but rather through release of increased tensile forces that drive acute disassociation of actin. 相似文献416.
Aruna Gowda Asha Ramanunni Carolyn Cheney Darlene Rozewski Wayne Kindsvoge Amy Lehman David Jarjoura Michael Caligiuri John C Byrd Natarajan Muthusamy 《MABS-AUSTIN》2010,2(1):35-41
CD4+ CD25+ regulatory Tt cells are expanded in solid and hematological malignancies including chronic lymphocytic leukemia (CLL). Several cytokines and co-stimulatory molecules are required for generation, survival and maintenance of their suppressive effect. We and others have shown direct cytotoxic effect of the novel common gamma chain cytokine interleukin (IL)-21 on primary B cells from CLL patients. Since members of this family of cytokines are known to exhibit their effects on diverse immune cells, we have examined the effects of IL-21 on CLL patient derived regulatory cell (Treg) induction, expansion and the inhibitory effect on natural killer cells in vitro. We demonstrate here the expression of IL-21 receptor in CD4+CD25High regulatory cells from CLL patients. In contrast to IL-2, the IL-21 cytokine failed to mediate expansion of regulatory cells or induced expression of Foxp3 in CD4+CD25Intermediate or CD4+CD25Dim/− cells in whole blood derived from CLL pat ients. Interestingly, in contrast to their differential effects on expansion of the CD4+CD25+Foxp3+T cells, IL-2 and IL-21 exhibited a redundant role in Ttreg mediated suppression of NK cell mediated antibody dependent cytotoxicity function. Given the infusion related toxicities and pro-survival effect of IL-2 in CLL, these studies provide a rationale to explore IL-21 as an alternate gamma chain cytokine in CLL therapy.Key words: chronic lymphocytic leukemia, IL-21, IL-2, immunosuppression, antibody dependent cellular cytotoxicity 相似文献
417.
418.
We performed a mutational analysis of the NS3 helicase of dengue virus to test insights gleaned from its crystal structure and identified four residues in the full-length protein that severely impaired either its RTPase and ATPase (Arg-457-458, Arg-460, Arg-463) or helicase (Ile-365, Arg-376) activity. Alanine substitution of Lys-396, which is located at the surface of domain II, drastically reduced all three enzymatic activities. Our study points to a pocket at the surface of domain II that may be suitable for the design of allosteric inhibitors. 相似文献
419.
420.
Pratibha Devarshi Aruna Kanase Ravindra Kanase Sadashiv Mane Subhash Patil A. T. Varute 《Journal of biosciences》1986,10(2):227-234
‘Mandur bhasma’, an ayurvedic preparation of iron is used in traditional medicine against hepatitis. In the present study
the hepatoprotective property of this drug was tested in albino rats during CC14 induced hepatic injury. The effect of mandur bhasma on the activities of the lipolytic enzymes of rat liver, kidney and adipose
tissue were studied during hepatitis induced by CCl4. The activities of acid lipase, alkaline lipase, lipoprotein lipase and hormone sensitive lipase exhibited significant alterations
during CCl4 induced hepatic injury, indicating a role for these enzymes in the mobilization of fat from adipose tissue and accumulation
of fat in liver and kidney. Simultaneous treatment with mandur bhasma prevented the paraffin mediated and CC14 mediated changes in the enzyme activities. These results suggest the hepatoprotective role of mandur bhasma during CCl4 induced hepatic injury. 相似文献