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121.
CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis 总被引:13,自引:0,他引:13
Teixeira-Clerc F Julien B Grenard P Tran Van Nhieu J Deveaux V Li L Serriere-Lanneau V Ledent C Mallat A Lotersztajn S 《Nature medicine》2006,12(6):671-676
Hepatic fibrosis, the common response associated with chronic liver diseases, ultimately leads to cirrhosis, a major public health problem worldwide. We recently showed that activation of hepatic cannabinoid CB2 receptors limits progression of experimental liver fibrosis. We also found that during the course of chronic hepatitis C, daily cannabis use is an independent predictor of fibrosis progression. Overall, these results suggest that endocannabinoids may drive both CB2-mediated antifibrogenic effects and CB2-independent profibrogenic effects. Here we investigated whether activation of cannabinoid CB1 receptors (encoded by Cnr1) promotes progression of fibrosis. CB1 receptors were highly induced in human cirrhotic samples and in liver fibrogenic cells. Treatment with the CB1 receptor antagonist SR141716A decreased the wound-healing response to acute liver injury and inhibited progression of fibrosis in three models of chronic liver injury. We saw similar changes in Cnr1-/- mice as compared to wild-type mice. Genetic or pharmacological inactivation of CB1 receptors decreased fibrogenesis by lowering hepatic transforming growth factor (TGF)-beta1 and reducing accumulation of fibrogenic cells in the liver after apoptosis and growth inhibition of hepatic myofibroblasts. In conclusion, our study shows that CB1 receptor antagonists hold promise for the treatment of liver fibrosis. 相似文献
122.
da Silva K Florentino LA da Silva KB de Brandt E Vandamme P de Souza Moreira FM 《Systematic and applied microbiology》2012,35(3):175-182
The aim of the present study was to identify a collection of 35 Cupriavidus isolates at the species level and to examine their capacity to nodulate and fix N(2). These isolates were previously obtained from the root nodules of two promiscuous trap species, Phaseolus vulgaris and Leucaena leucocephala, inoculated with soil samples collected near Sesbania virgata plants growing in Minas Gerais (Brazil) pastures. Phenotypic and genotypic methods applied for this study were SDS-PAGE of whole-cell proteins, and 16S rRNA and gyrB gene sequencing. To confirm the ability to nodulate and fix N(2), the presence of the nodC and nifH genes was also determined, and an experiment was carried out with two representative isolates in order to authenticate them as legume nodule symbionts. All 35 isolates belonged to the betaproteobacterium Cupriavidus necator, they possessed the nodC and nifH genes, and two representative isolates were able to nodulate five different promiscuous legume species: Mimosa caesalpiniaefolia, L. leucocephala, Macroptilium atropurpureum, P. vulgaris and Vigna unguiculata. This is the first study to demonstrate that C. necator can nodulate legume species. 相似文献
123.
Disruption of cholesterol metabolism has been hypothesized to contribute to dementia, possibly due to its role in maintaining
membrane fluidity as well as the integrity of lipid rafts. Previously, we reported an apparent inverse relationship between
membrane cholesterol levels and those of GM1, another lipid that can be found in rafts. This paper describes the observation
that red blood cell (RBC) membranes isolated from blood drawn from children diagnosed with autism have on the average significantly
less cholesterol and significantly more GM1 than RBC membranes isolated from blood obtained from control children. While cholesterol
in the circulation does not cross the blood brain barrier, a generalized defect in its synthesis could affect its concentration
in the central nervous system and that, coupled with a change in ganglioside expression, could contribute to development of
the behaviors associated with autism. 相似文献
124.
Brodehl A Hedde PN Dieding M Fatima A Walhorn V Gayda S Šarić T Klauke B Gummert J Anselmetti D Heilemann M Nienhaus GU Milting H 《The Journal of biological chemistry》2012,287(19):16047-16057
Mutations in the DES gene coding for the intermediate filament protein desmin may cause skeletal and cardiac myopathies, which are frequently characterized by cytoplasmic aggregates of desmin and associated proteins at the cellular level. By atomic force microscopy, we demonstrated filament formation defects of desmin mutants, associated with arrhythmogenic right ventricular cardiomyopathy. To understand the pathogenesis of this disease, it is essential to analyze desmin filament structures under conditions in which both healthy and mutant desmin are expressed at equimolar levels mimicking an in vivo situation. Here, we applied dual color photoactivation localization microscopy using photoactivatable fluorescent proteins genetically fused to desmin and characterized the heterozygous status in living cells lacking endogenous desmin. In addition, we applied fluorescence resonance energy transfer to unravel short distance structural patterns of desmin mutants in filaments. For the first time, we present consistent high resolution data on the structural effects of five heterozygous desmin mutations on filament formation in vitro and in living cells. Our results may contribute to the molecular understanding of the pathological filament formation defects of heterozygous DES mutations in cardiomyopathies. 相似文献
125.
Rabe Bernhardt N Memic F Gezelius H Thiebes AL Vallstedt A Kullander K 《Developmental biology》2012,366(2):279-289
Coordinated limb rhythmic movements take place through organized signaling in local spinal cord neuronal networks. The establishment of these circuitries during development is dependent on the correct guidance of axons to their targets. It has previously been shown that the well-known axon guidance molecule netrin-1 is required for configuring the circuitry that provides left-right alternating coordination in fictive locomotion. The attraction of commissural axons to the midline in response to netrin-1 has been shown to involve the netrin-1 receptor DCC (deleted in Colorectal Cancer). However, the role of DCC for the establishment of CPG coordination has not yet been resolved. We show that mice carrying a null mutation of DCC displayed an uncoordinated left-right activity during fictive locomotion accompanied by a loss of interneuronal subpopulations originating from commissural progenitors. Thus, DCC plays a crucial role in the formation of spinal neuronal circuitry coordinating left-right activities. Together with the previously published results from netrin-1 deficient mice, the data presented in this study suggest a role for the most ventral originating V3 interneurons in synchronous activities over the midline. Further, it provides evidence that axon crossing in the spinal cord is more intricately controlled than in previously suggested models of DCC-netrin-1 interaction. 相似文献
126.
Seguin-Py S Lucchi G Croizier S Chakrama FZ Despouy G Le Grand JN Ducoroy P Boireau W Boyer-Guittaut M Jouvenot M Fraichard A Delage-Mourroux R 《Biochimie》2012,94(3):748-758
GABARAPL1 belongs to the small family of GABARAP proteins (including GABARAP, GABARAPL1 and GABARAPL2/GATE-16), one of the two subfamilies of the yeast Atg8 orthologue. GABARAPL1 is involved in the intracellular transport of receptors, via an interaction with tubulin and GABA(A) or kappa opioid receptors, and also participates in autophagy and cell proliferation. In the present study, we identify the HSP90 protein as a novel interaction partner for GABARAPL1 using GST pull-down, mass spectrometry and coimmunoprecipitation experiments. GABARAPL1 and HSP90 partially colocalize in MCF-7 breast cancer cells overexpressed Dsred-GABARAPL1 and in rat brain. Moreover, treatment of MCF-7 cells overexpressed FLAG-GABARAPL1-6HIS with the HSP90 inhibitor 17-AAG promotes the GABARAPL1 degradation, a process that is blocked by proteasome inhibitors such as MG132, bortezomib and lactacystin. Accordingly, we demonstrate that HSP90 interacts and protects GABARAPL1 from its degradation by the proteasome. 相似文献
127.
Nik-Zainal S Alexandrov LB Wedge DC Van Loo P Greenman CD Raine K Jones D Hinton J Marshall J Stebbings LA Menzies A Martin S Leung K Chen L Leroy C Ramakrishna M Rance R Lau KW Mudie LJ Varela I McBride DJ Bignell GR Cooke SL Shlien A Gamble J Whitmore I Maddison M Tarpey PS Davies HR Papaemmanuil E Stephens PJ McLaren S Butler AP Teague JW Jönsson G Garber JE Silver D Miron P Fatima A Boyault S Langerød A Tutt A Martens JW Aparicio SA Borg Å Salomon AV Thomas G Børresen-Dale AL Richardson AL 《Cell》2012,149(5):979-993
128.
S El Abed SK Ibnsouda H Latrache H Meftah NJ Tahri F Hamadi 《World journal of microbiology & biotechnology》2012,28(4):1707-1713
Initial microbial adhesion to surfaces is a complicated process that is affected by a number of factors. An important property of a solution that may influence adhesion is pH. The surface properties of the cedar wood were characterized by the sessile drop technique. Moreover, the interfacial free energy of surface adhesion to the cedar wood was determined under pH values (2, 3, 5, 7, 9 and 11). The results showed that cedar wood examined at different pH levels could be considered hydrophobic ranged from Giwi = ?13.1 mJ/m2 to Giwi = ?75 mJ/m2. We noted that the electron-donor character of cedar wood was important at both basic and limit acidic conditions (pH 11 and pH 3) and it decreased at intermediate pH (pH 5). The cedar wood substratum presents a weak electron acceptor under various pH’s. In addition, the adhesion of conidia from Penicilllium expansum to the cedar wood surfaces at different pH values (2, 3, 5, 7, 9 and 11) was investigated using Environmental Scanning Electron Microscopy and image analysis was assessed with the Mathlab® program. The data analysis showed that the conidia from P. expansum were strongly influenced by the pH. The maximum adhesion occurs in the pH 11 and pH 3 and decreased to 24% at pH 5. 相似文献
129.
PA Avelar Ferreira CA Bomfeti B Lima Soares FM de Souza Moreira 《World journal of microbiology & biotechnology》2012,28(5):1947-1959
One of the most cultivated and consumed vegetables in Brazil is the common bean, Phaseolus vulgaris L. The symbiosis of this plant species with nitrogen-fixing bacteria that are adapted to the stresses commonly found in tropical
soils can increase production. The aim of this study was to evaluate the symbiotic effectiveness of bacterial strains from
soils under different land uses in the Amazon region. Further, rhizobia tolerance to acidity and aluminium and the involvement
of some possible physiological mechanisms of such tolerance were also investigated. In assessing the efficiency of biological
nitrogen fixation, inoculation with strains UFLA04-195, UFLA04-173 and UFLA04-202, belonging to the genus Rhizobium, resulted in greater plant growth, higher shoot nitrogen content and good nodulation compared to the inoculation with the
strain CIAT 899 (R. tropici), and to the mineral nitrogen control or Burkholderia fungorum strains that nodulated or not bean plants. These efficient strains grew better at pH 5.0 than at pH 6.0 or pH 6.9; they also
tolerated up to 1 mmol l−1 of Al3+ and showed an increased production of exopolysaccharides where the growing rates were less (pH 6.0 and pH 6.9). With respect
to aluminium, the highest production of EPS produced greater tolerance to this element. Taken together, these results indicate
that the strains evaluated in this study were tolerant to acidity and aluminium; they appeared to have developed resistance
mechanisms such as EPS production and a resistant cell outer membrane (indicated by resistance to polymyxin and methyl violet).
As these strains also gave increased yields of the host species, further studies on whether to recommend these strains as
inoculants are already underway. 相似文献
130.
Leandro Marciano Marra Cláudio Roberto Fonsêca Sousa Soares Silvia Maria de Oliveira Paulo Ademar Avelar Ferreira Bruno Lima Soares Renato de Fráguas Carvalho José Maria de Lima Fatima Maria de Souza Moreira 《Plant and Soil》2012,357(1-2):289-307