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941.
Diogo M. Geraldes Luca Modenese Andrew T. M. Phillips 《Biomechanics and modeling in mechanobiology》2016,15(5):1029-1042
Functional adaptation of the femur has been investigated in several studies by embedding bone remodelling algorithms in finite element (FE) models, with simplifications often made to the representation of bone’s material symmetry and mechanical environment. An orthotropic strain-driven adaptation algorithm is proposed in order to predict the femur’s volumetric material property distribution and directionality of its internal structures within a continuum. The algorithm was applied to a FE model of the femur, with muscles, ligaments and joints included explicitly. Multiple load cases representing distinct frames of two activities of daily living (walking and stair climbing) were considered. It is hypothesised that low shear moduli occur in areas of bone that are simply loaded and high shear moduli in areas subjected to complex loading conditions. In addition, it is investigated whether material properties of different femoral regions are stimulated by different activities. The loading and boundary conditions were considered to provide a physiological mechanical environment. The resulting volumetric material property distribution and directionalities agreed with ex vivo imaging data for the whole femur. Regions where non-orthogonal trabecular crossing has been documented coincided with higher values of predicted shear moduli. The topological influence of the different activities modelled was analysed. The influence of stair climbing on the properties of the femoral neck region is highlighted. It is recommended that multiple load cases should be considered when modelling bone adaptation. The orthotropic model of the complete femur is released with this study. 相似文献
942.
Sonia Altizer Keith A. Hobson Andrew K. Davis Jacobus C. De Roode Leonard I. Wassenaar 《PloS one》2015,10(11)
Long-distance migration can lower parasite prevalence if strenuous journeys remove infected animals from wild populations. We examined wild monarch butterflies (Danaus plexippus) to investigate the potential costs of the protozoan Ophryocystis elektroscirrha on migratory success. We collected monarchs from two wintering sites in central Mexico to compare infection status with hydrogen isotope (δ
2H) measurements as an indicator of latitude of origin at the start of fall migration. On average, uninfected monarchs had lower δ
2H values than parasitized butterflies, indicating that uninfected butterflies originated from more northerly latitudes and travelled farther distances to reach Mexico. Within the infected class, monarchs with higher quantitative spore loads originated from more southerly latitudes, indicating that heavily infected monarchs originating from farther north are less likely to reach Mexico. We ruled out the alternative explanation that lower latitudes give rise to more infected monarchs prior to the onset of migration using citizen science data to examine regional differences in parasite prevalence during the summer breeding season. We also found a positive association between monarch wing area and estimated distance flown. Collectively, these results emphasize that seasonal migrations can help lower infection levels in wild animal populations. Our findings, combined with recent declines in the numbers of migratory monarchs wintering in Mexico and observations of sedentary (winter breeding) monarch populations in the southern U.S., suggest that shifts from migratory to sedentary behavior will likely lead to greater infection prevalence for North American monarchs. 相似文献
943.
Mohammed Mamdani Vernell Williamson Gowon O. McMichael Tana Blevins Fazil Aliev Amy Adkins Laura Hack Tim Bigdeli Andrew D. van der Vaart Bradley Todd Web Silviu-Alin Bacanu Gursharan Kalsi COGA Consortium Kenneth S. Kendler Michael F. Miles Danielle Dick Brien P. Riley Catherine Dumur Vladimir I. Vladimirov 《PloS one》2015,10(9)
944.
Andrew Chay Ilaria Zamparo Andreas Koschinski Manuela Zaccolo Kim T. Blackwell 《PLoS computational biology》2016,12(2)
Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory. 相似文献
945.
946.
Anton A. Buzdin Alina V. Artcibasova Natalya F. Fedorova Maria V. Suntsova Andrew V. Garazha Maxim I. Sorokin 《Cell cycle (Georgetown, Tex.)》2016,15(24):3378-3389
Responses to human cytomegalovirus (HCMV) infection are largely individual and cell type specific. We investigated molecular profiles in 2 primary cell cultures of human fibroblasts, which are highly or marginally sensitive to HCMV infection, respectively. We screened expression of genes and microRNAs (miRs) at the early (3 hours) stage of infection. To assess molecular pathway activation profiles, we applied bioinformatic algorithms OncoFinder and MiRImpact. In both cell types, pathway regulation properties at mRNA and miR levels were markedly different. Surprisingly, in the infected highly sensitive cells, we observed a “freeze” of miR expression profiles compared to uninfected controls. Our results evidence that in the sensitive cells, HCMV blocks intracellular regulation of microRNA expression already at the earliest stage of infection. These data suggest somewhat new functions for HCMV products and demonstrate dependence of miR expression arrest on the host-encoded factors. 相似文献
947.
DnaJ/Hsc70 chaperone complexes control the extracellular release of neurodegenerative‐associated proteins 下载免费PDF全文
Dali Zheng Dale Chaput April Darling Justin H Trotter Andrew R Stothert Bryce A Nordhues April Lussier Jeremy Baker Lindsey Shelton Mahnoor Kahn Laura J Blair Stanley M Stevens Jr Chad A Dickey 《The EMBO journal》2016,35(14):1537-1549
It is now known that proteins associated with neurodegenerative disease can spread throughout the brain in a prionlike manner. However, the mechanisms regulating the trans‐synaptic spread propagation, including the neuronal release of these proteins, remain unknown. The interaction of neurodegenerative disease‐associated proteins with the molecular chaperone Hsc70 is well known, and we hypothesized that much like disaggregation, refolding, degradation, and even normal function, Hsc70 may dictate the extracellular fate of these proteins. Here, we show that several proteins, including TDP‐43, α‐synuclein, and the microtubule‐associated protein tau, can be driven out of the cell by an Hsc70 co‐chaperone, DnaJC5. In fact, DnaJC5 overexpression induced tau release in cells, neurons, and brain tissue, but only when activity of the chaperone Hsc70 was intact and when tau was able to associate with this chaperone. Moreover, release of tau from neurons was reduced in mice lacking the DnaJC5 gene and when the complement of DnaJs in the cell was altered. These results demonstrate that the dynamics of DnaJ/Hsc70 complexes are critically involved in the release of neurodegenerative disease proteins. 相似文献
948.
Olivier Koole Julie A Denison Joris Menten Sharon Tsui Fred Wabwire-Mangen Gideon Kwesigabo Modest Mulenga Andrew Auld Simon Agolory Ya Diul Mukadi Eric van Praag Kwasi Torpey Seymour Williams Jonathan Kaplan Aaron Zee David R Bangsberg Robert Colebunders 《PloS one》2016,11(1)
Objectives
To identify the reasons patients miss taking their antiretroviral therapy (ART) and the proportion who miss their ART because of symptoms; and to explore the association between symptoms and incomplete adherence.Methods
Secondary analysis of data collected during a cross-sectional study that examined ART adherence among adults from 18 purposefully selected sites in Tanzania, Uganda, and Zambia. We interviewed 250 systematically selected patients per facility (≥18 years) on reasons for missing ART and symptoms they had experienced (using the HIV Symptom Index). We abstracted clinical data from the patients’ medical, pharmacy, and laboratory records. Incomplete adherence was defined as having missed ART for at least 48 consecutive hours during the past 3 months.Results
Twenty-nine percent of participants reported at least one reason for having ever missed ART (1278/4425). The most frequent reason was simply forgetting (681/1278 or 53%), followed by ART-related hunger or not having enough food (30%), and symptoms (12%). The median number of symptoms reported by participants was 4 (IQR: 2–7). Every additional symptom increased the odds of incomplete adherence by 12% (OR: 1.1, 95% CI: 1.1–1.2). Female participants and participants initiated on a regimen containing stavudine were more likely to report greater numbers of symptoms.Conclusions
Symptoms were a common reason for missing ART, together with simply forgetting and food insecurity. A combination of ART regimens with fewer side effects, use of mobile phone text message reminders, and integration of food supplementation and livelihood programmes into HIV programmes, have the potential to decrease missed ART and hence to improve adherence and the outcomes of ART programmes. 相似文献949.
Angela M. Mech Kathryn A. Thomas Travis D. Marsico Daniel A. Herms Craig R. Allen Matthew P. Ayres Kamal J. K. Gandhi Jessica Gurevitch Nathan P. Havill Ruth A. Hufbauer Andrew M. Liebhold Kenneth F. Raffa Ashley N. Schulz Daniel R. Uden Patrick C. Tobin 《Ecology and evolution》2019,9(21):12216-12230
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950.
Andrew T Templin Bernhard Maier Yurika Nishiki Sarah A Tersey Raghavendra G Mirmira 《Cell cycle (Georgetown, Tex.)》2011,10(7):1043-1049
Deoxyhypusine synthase (DHS) catalyzes the post-translational formation of the amino acid hypusine. Hypusine is unique to the eukaryotic translational initiation factor 5A (eIF5A), and is required for its functions in mRNA shuttling, translational elongation and stress granule formation. In recent studies, we showed that DHS promotes cytokine and ER stress signaling in the islet β cell and thereby contributes to its dysfunction in the setting of diabetes mellitus. Here, we review the evidence supporting a role for DHS (and hypusinated eIF5A) in cellular stress responses, and provide new data on the phenotype of DHS knockout mice. We show that homozygous knockout mice are embryonic lethal, but heterozygous knockout mice appear normal with no evidence of growth or metabolic deficiencies. Mouse embryonic fibroblasts from heterozygous knockout mice attenuate acute cytokine signaling, as evidenced by reduced production of inducible nitric oxide synthase, but show no statistically significant defects in proliferation or cell cycle progression. Our data are discussed with respect to the utility of sub- maximal inhibition of DHS in the setting of inflammatory states, such as diabetes mellitus.Key words: inflammation, post-translational modification, cytokine, diabetes, mRNA translation, hypusine 相似文献