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991.
Common and distinct patterns of terminal modifications to mirtrons and canonical microRNAs 总被引:1,自引:0,他引:1
Nucleotide modifications to microRNAs or their precursors can influence their processing and/or activity. A challenge to their analysis is the lack of independent references for the termini generated by primary processing; typically, these are empirically assigned as the most abundant mapped reads. Mirtrons offer such an independent measure since these microRNA hairpins are defined by splicing. Consequently, mirtron-derived reads that deviate from splice sites reflect modification following primary processing. Analysis in Drosophila revealed multiple modification patterns, including select alterations of 5' termini, many 3' resection events, and unexpectedly abundant 3' untemplated monouridylation. Resections occur on mature AGO1-loaded species, whereas uridylation occurs on pre-miRNAs but is compatible with dicing and AGO1 loading. Strikingly, we found many mirtrons whose modified reads are more abundant than those produced by primary processing. In some cases, these abundant modified reads matched the genome owing to fortuitous uridines in downstream flanking exons, thus highlighting the value of an independent reference for the primary-processed sequence. We could further extend the principle of abundant and preferred uridylation of mirtrons, relative to canonical pre-miRNAs, to Caenorhabditis elegans, mouse, and human. Finally, we found that 3' resection occurs broadly across AGO1-loaded canonical miRNA and star species. Altogether, these findings substantially broaden the complexity of terminal modification pathways acting upon small regulatory RNAs. 相似文献
992.
993.
Because viral replication depends on the vigour of its host, many viruses have evolved incentives of fitness to pay their keep. When the viral host is a human pathogen, these fitness factors can surface as virulence: creating a Russian doll of pathogenesis where pathogens within pathogens complicate the disease process. Microbial viruses can even be independently immunogenic, as we recently reported for leishmania-virus. Thus, the incidence of this 'hyperpathogenism' is becoming an important clinical consideration and by appreciating the microbial-virus as a backseat driver of human disease, we could exploit its presence as a diagnostic biomarker and molecular target for therapeutic intervention. Here we discuss the prevalence of clinically relevant hyperpathogenism as well as the environmental sanctuaries that breed it. 相似文献
994.
Souha Berriri Ana Victoria Garcia Nicolas Frei dit Frey Wilfried Rozhon Stéphanie Pateyron Nathalie Leonhardt Jean-Luc Montillet Jeffrey Leung Heribert Hirt Jean Colcombet 《The Plant cell》2012,24(10):4281-4293
Plant mitogen-activated protein kinases (MAPKs) are involved in important processes, including stress signaling and development. In a functional yeast screen, we identified mutations that render Arabidopsis thaliana
MAPKs constitutively active (CA). Importantly, CA-MAPKs maintain their specificity toward known activators and substrates. As a proof-of-concept, Arabidopsis MAPK4 (MPK4) function in plant immunity was investigated. In agreement with the phenotype of mpk4 mutants, CA-MPK4 plants were compromised in pathogen-induced salicylic acid accumulation and disease resistance. MPK4 activity was found to negatively regulate pathogen-associated molecular pattern-induced reactive oxygen species production but had no impact on callose deposition, indicating that CA-MPK4 allows discriminating between processes regulated by MPK4 activity from processes indirectly affected by mpk4 mutation. Finally, MPK4 activity was also found to compromise effector-triggered immunity conditioned by the Toll Interleukin-1 Receptor–nucleotide binding (NB)–Leu-rich repeat (LRR) receptors RPS4 and RPP4 but not by the coiled coil–NB-LRR receptors RPM1 and RPS2. Overall, these data reveal important insights on how MPK4 regulates plant defenses and establishes that CA-MAPKs offer a powerful tool to analyze the function of plant MAPK pathways. 相似文献
995.
The superfamily Testudinoidea is the most diverse and widely distributed clade of extant turtles. Surprisingly, despite an extensive fossil record, and increasing amount of molecular data available, the temporal origin of this group is still largely unknown. To address this issue, we used a comprehensive molecular dataset to perform phylogenetic and molecular dating analyses, as well as seven fossil constraints to calibrate the ages of the nodes in the phylogeny. The molecular dataset includes the complete mitochondrial genomes of 37 turtle species, including newly sequenced mitochondrial genomes of Phrynops hilarii, Emys orbicularis, Rhinoclemmys punctularia, and Chelonoidis nigra, and four nuclear markers. Our results revealed that the earliest divergences within crown testudinoids occurred around 95.0 Mya, in the early Late Cretaceous, earlier than previously reported, raising new questions about the historical biogeography of this group. 相似文献
996.
997.
TLR2 and TLR4 activation induces p38 MAPK‐dependent phosphorylation of S6 kinase 1 in C2C12 myotubes
Hermann Zbinden‐Foncea Louise Deldicque Nicolas Pierre Marc Francaux Jean‐Marc Raymackers 《Cell biology international》2012,36(12):1107-1113
Toll‐like receptors 2 (TLR2) and 4 (TLR4) are present in the plasma membrane of skeletal muscle cells where their functions remain incompletely resolved. They can bind various extracellular ligands, such as FSL‐1, lipopolysaccharide (LPS) and/or palmitic acid (PA). We have investigated the link between PA, TLR2/4 and ribosomal S6 kinase 1 (S6K1) in C2C12 myotubes. Incubation with agonists of either TLR2 or TLR4, and with a high concentration of PA, increased S6K1 phosphorylation. Canonical upstream kinases of S6K1, protein kinase B (PKB) and mammalian target of rapamycin complex 1 (mTORC1), were regulated in the opposite way by PA, indicating that these kinases were probably not involved. By using the SB202190 inhibitor, p38 MAPK (mitogen‐activated protein kinase) was found to be a key mediator of PA‐induced phosphorylation of S6K1. Downregulation of either tlr2 or tlr4 gene expression by small interfering RNAs prevented the activation of both p38 MAPK and S6K1 by FSL‐1, LPS or PA. Thus TLR2 and TLR4 agonists can increase the level of S6K1 phosphorylation in a p38 MAPK‐dependent way in C2C12 myotubes. As PA induced the same intracellular signalling, a novel atypical pathway for PA is induced at the cellular membrane level and results in a higher phosphorylation state of S6K1. 相似文献
998.
Theoretical and empirical work indicates that the central nervous system is able to stabilize motor performance by selectively suppressing task-relevant variability (TRV), while allowing task-equivalent variability (TEV) to occur. During unperturbed bipedal standing, it has previously been observed that, for task variables such as the whole-body center of mass (CoM), TEV exceeds TRV in amplitude. However, selective control (and correction) of TRV should also lead to different temporal characteristics, with TEV exhibiting higher temporal persistence compared to TRV. The present study was specifically designed to test this prediction. Kinematics of prolonged quiet standing (5 minutes) was measured in fourteen healthy young participants, with eyes closed. Using the uncontrolled manifold analysis, postural variability in six sagittal joint angles was decomposed into TEV and TRV with respect to four task variables: (1) center of mass (CoM) position, (2) head position, (3) trunk orientation and (4) head orientation. Persistence of fluctuations within the two variability components was quantified by the time-lagged auto-correlation, with eight time lags between 1 and 128 seconds. The pattern of results differed between task variables. For three of the four task variables (CoM position, head position, trunk orientation), TEV significantly exceeded TRV over the entire 300 s-period.The autocorrelation analysis confirmed our main hypothesis for CoM position and head position: at intermediate and longer time delays, TEV exhibited higher persistence than TRV. Trunk orientation showed a similar trend, while head orientation did not show a systematic difference between TEV and TRV persistence. The combination of temporal and task-equivalent analyses in the present study allow a refined characterization of the dynamic control processes underlying the stabilization of upright standing. The results confirm the prediction, derived from computational motor control, that task-equivalent fluctuations for specific task variables show higher temporal persistence compared to task-relevant fluctuations. 相似文献
999.
David Nanchen Nicolas Rodondi Jacques Cornuz Teresa Hillier Kristine E. Ensrud Jane A. Cauley Douglas C. Bauer Study of Osteoporotic Fractures Research Group 《PloS one》2012,7(11)
Background
Current guidelines for the prevention of cardiovascular disease (CVD) recommend diabetes as a CVD risk equivalent. However, reports that have examined the risk of diabetes in comparison to pre-existing CVD are lacking among older women. We aimed to assess whether diabetes was associated with a similar risk of total and cause-specific mortality as a history of CVD in older women.Methodology/Principal Findings
We studied 9218 women aged 68 years or older enrolled in a prospective cohort study (Study of Osteoporotic Fracture) during a mean follow-up period of 11.7 years and compared all-cause, cardiovascular and coronary heart disease mortality among 4 groups: non-diabetic women with and without existing CVD, diabetic women with and without existing CVD. Mean (SD) age of the participants was 75.2 (5.3) years, 3.5% reported diabetes and 6.8% reported existing CVD. During follow-up, 5117 women died with 36% from CVD. The multivariate adjusted risk of cardiovascular mortality was increased among both non-diabetic women with CVD (hazard ratio (HR) 2.32, 95% CI: 1.97–2.74, P<0.001) and diabetic women without CVD (HR 2.06, CI: 1.62–2.64, P<0.001) compared to non-diabetic women without existing CVD. All-cause, cardiovascular and coronary mortality of non-diabetic women with CVD were not significantly different from diabetic women without CVD.Conclusions/Significance
Older diabetic women without CVD have a similar risk of cardiovascular mortality compared to non-diabetic women with pre-existing CVD. The equivalence of diabetes and CVD seems to extend to older women, supporting current guidelines for cardiovascular prevention. 相似文献1000.
Sophie Perrin Jonathan Cremer Olivia Faucher Jacques Reynes Pierre Dellamonica Jo?lle Micallef Caroline Solas Bruno Lacarelle Charlotte Stretti Elise Kaspi Andrée Robaglia-Schlupp Corine Nicolino-Brunet Catherine Tamalet Nicolas Lévy Isabelle Poizot-Martin Pierre Cau Patrice Roll 《PloS one》2012,7(12)