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891.
John W Simmons Kevin K Chung Evan M Renz Christopher E White Casey L Cotant Molly A Tilley Mark O Hardin John A Jones Lorne H Blackbourne Steven E Wolf 《BMC anesthesiology》2010,10(1):1-7
Background
We sought to evaluate agreement between a new and widely implemented method of temperature measurement in critical care, temporal artery thermometry and an established method of core temperature measurement, bladder thermometry as performed in clinical practice.Methods
Temperatures were simultaneously recorded hourly (n = 736 observations) using both devices as part of routine clinical monitoring in 14 critically ill adult patients with temperatures ranging ≥1°C prior to consent.Results
The mean difference between temporal artery and bladder temperatures measured was -0.44°C (95% confidence interval, -0.47°C to -0.41°C), with temporal artery readings lower than bladder temperatures. Agreement between the two devices was greatest for normothermia (36.0°C to < 38.3°C) (mean difference -0.35°C [95% confidence interval, -0.37°C to -0.33°C]). The temporal artery thermometer recorded higher temperatures during hypothermia (< 36°C) (mean difference 0.66°C [95% confidence interval, 0.53°C to 0.79°C]) and lower temperatures during hyperthermia (≥38.3°C) (mean difference -0.90°C [95% confidence interval, -0.99°C to -0.81°C]). The sensitivity for detecting fever (core temperature ≥38.3°C) using the temporal artery thermometer was 0.26 (95% confidence interval, 0.20 to 0.33), and the specificity was 0.99 (95% confidence interval, 0.98 to 0.99). The positive likelihood ratio for fever was 24.6 (95% confidence interval, 10.7 to 56.8); the negative likelihood ratio was 0.75 (95% confidence interval, 0.68 to 0.82).Conclusions
Temporal artery thermometry produces somewhat surprising disagreement with an established method of core temperature measurement and should not to be used in situations where body temperature needs to be measured with accuracy. 相似文献892.
Thanemozhi G Natarajan Bhaskar V Kallakury Christine E Sheehan Margaret B Bartlett Natarajan Ganesan Anju Preet Jeffrey S Ross Kevin T FitzGerald 《Cancer cell international》2010,10(1):13
Background
MLL2, an epigenetic regulator in mammalian cells, mediates histone 3 lysine 4 tri-methylation (H3K4me3) through the formation of a multiprotein complex. MLL2 shares a high degree of structural similarity with MLL, which is frequently disrupted in leukemias via chromosomal translocations. However, this structural similarity is not accompanied by functional equivalence. In light of this difference, and previous reports on involvement of epigenetic regulators in malignancies, we investigated MLL2 expression in established cell lines from breast and colon tissues. We then investigated MLL2 in solid tumors of breast and colon by immunohistochemistry, and evaluated potential associations with established clinicopathologic variables. 相似文献893.
Isabelle St-Louis Mohan Singh Kevin Brasseur Valérie Leblanc Sophie Parent Eric Asselin 《Reproductive biology and endocrinology : RB&E》2010,8(1):103
Background
Cyclooxygenases (COXs) are the rate limiting enzymes in the process of prostaglandins (PGs) synthesis, which are critical regulators of a number of reproductive processes, including ovulation, implantation, decidualization and parturition. The aim of the present study was to investigate the expression and regulation of COX-1 and COX-2 and levels of prostaglandins during rat pregnancy, in a model of pseudopregnancy and estrous cycle. 相似文献894.
Jennifer W. Hill Carol F. Elias Makoto Fukuda Kevin W. Williams Eric D. Berglund William L. Holland You-Ree Cho Jen-Chieh Chuang Yong Xu Michelle Choi Danielle Lauzon Charlotte E. Lee Roberto Coppari James A. Richardson Jeffrey M. Zigman Streamson Chua Philipp E. Scherer Bradford B. Lowell Jens C. Brüning Joel K. Elmquist 《Cell metabolism》2010,11(4):286-297
895.
Kevin N. Couper Tom Barnes Julius C. R. Hafalla Valery Combes Bernhard Ryffel Thomas Secher Georges E. Grau Eleanor M. Riley J. Brian de Souza 《PLoS pathogens》2010,6(1)
There is considerable debate as to the nature of the primary parasite-derived moieties that activate innate pro-inflammatory responses during malaria infection. Microparticles (MPs), which are produced by numerous cell types following vesiculation of the cellular membrane as a consequence of cell death or immune-activation, exert strong pro-inflammatory activity in other disease states. Here we demonstrate that MPs, derived from the plasma of malaria infected mice, but not naive mice, induce potent activation of macrophages in vitro as measured by CD40 up-regulation and TNF production. In vitro, these MPs induced significantly higher levels of macrophage activation than intact infected red blood cells. Immunofluorescence staining revealed that MPs contained significant amounts of parasite material indicating that they are derived primarily from infected red blood cells rather than platelets or endothelial cells. MP driven macrophage activation was completely abolished in the absence of MyD88 and TLR-4 signalling. Similar levels of immunogenic MPs were produced in WT and in TNF−/−, IFN-γ−/−, IL-12−/− and RAG-1−/− malaria-infected mice, but were not produced in mice injected with LPS, showing that inflammation is not required for the production of MPs during malaria infection. This study therefore establishes parasitized red blood cell-derived MPs as a major inducer of systemic inflammation during malaria infection, raising important questions about their role in severe disease and in the generation of adaptive immune responses. 相似文献
896.
897.
Myeloid dendritic cells (mDC) are lost from blood in individuals with human immunodeficiency virus (HIV) infection but the mechanism for this loss and its relationship to disease progression are not known. We studied the mDC response in blood and lymph nodes of simian immunodeficiency virus (SIV)-infected rhesus macaques with different disease outcomes. Early changes in blood mDC number were inversely correlated with virus load and reflective of eventual disease outcome, as animals with stable infection that remained disease-free for more than one year had average increases in blood mDC of 200% over preinfection levels at virus set-point, whereas animals that progressed rapidly to AIDS had significant loss of mDC at this time. Short term antiretroviral therapy (ART) transiently reversed mDC loss in progressor animals, whereas discontinuation of ART resulted in a 3.5-fold increase in mDC over preinfection levels only in stable animals, approaching 10-fold in some cases. Progressive SIV infection was associated with increased CCR7 expression on blood mDC and an 8-fold increase in expression of CCL19 mRNA in lymph nodes, consistent with increased mDC recruitment. Paradoxically, lymph node mDC did not accumulate in progressive infection but rather died from caspase-8-dependent apoptosis that was reduced by ART, indicating that increased recruitment is offset by increased death. Lymph node mDC from both stable and progressor animals remained responsive to exogenous stimulation with a TLR7/8 agonist. These data suggest that mDC are mobilized in SIV infection but that an increase in the CCR7-CCL19 chemokine axis associated with high virus burden in progressive infection promotes exodus of activated mDC from blood into lymph nodes where they die from apoptosis. We suggest that inflamed lymph nodes serve as a sink for mDC through recruitment, activation and death that contributes to AIDS pathogenesis. 相似文献
898.
Blair WS Pickford C Irving SL Brown DG Anderson M Bazin R Cao J Ciaramella G Isaacson J Jackson L Hunt R Kjerrstrom A Nieman JA Patick AK Perros M Scott AD Whitby K Wu H Butler SL 《PLoS pathogens》2010,6(12):e1001220
Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that directly target HIV-1 capsid (CA) via a novel mechanism of action. The compounds exhibit potent antiviral activity against HIV-1 laboratory strains, clinical isolates, and HIV-2, and inhibit both early and late events in the viral replication cycle. We present mechanistic studies indicating that these early and late activities result from the compound affecting viral uncoating and assembly, respectively. We show that amino acid substitutions in the N-terminal domain of HIV-1 CA are sufficient to confer resistance to this class of compounds, identifying CA as the target in infected cells. A high-resolution co-crystal structure of the compound bound to HIV-1 CA reveals a novel binding pocket in the N-terminal domain of the protein. Our data demonstrate that broad-spectrum antiviral activity can be achieved by targeting this new binding site and reveal HIV CA as a tractable drug target for HIV therapy. 相似文献
899.
Diego del Alamo Kevin L. Jagessar Jens Meiler Hassane S. Mchaourab 《PLoS computational biology》2021,17(6)
We describe an approach for integrating distance restraints from Double Electron-Electron Resonance (DEER) spectroscopy into Rosetta with the purpose of modeling alternative protein conformations from an initial experimental structure. Fundamental to this approach is a multilateration algorithm that harnesses sets of interconnected spin label pairs to identify optimal rotamer ensembles at each residue that fit the DEER decay in the time domain. Benchmarked relative to data analysis packages, the algorithm yields comparable distance distributions with the advantage that fitting the DEER decay and rotamer ensemble optimization are coupled. We demonstrate this approach by modeling the protonation-dependent transition of the multidrug transporter PfMATE to an inward facing conformation with a deviation to the experimental structure of less than 2Å Cα RMSD. By decreasing spin label rotamer entropy, this approach engenders more accurate Rosetta models that are also more closely clustered, thus setting the stage for more robust modeling of protein conformational changes. 相似文献
900.
Serlin Bruce S.; Lew Roger R.; Krasnoshtein Flora; Krol Justyna; Sumida Kevin D. 《Plant & cell physiology》1996,37(2):175-179
Red light mediates chloroplast movement and increased activityof calcium-activated potassium channels on the plasma membraneof the alga Mougeotia sp. (UTEX LB 734). When activation ismediated by phytochrome, a far-red light irradiation given sometime after the red light irradiation will reverse the effectof the red light, due to phytochrome photoreversibility. Wecharacterized the escape times (time required for loss of photoreversibility)for these two processes to compare the transduction pathwaysinvolved in chloroplast rotation and channel activation. Theescape time for chloroplast rotation was 2.5 min after red lightirradiation (red and far-red light irradiations were 30 s).For channel activation, shorter red and far-red light irradiations(10 s) had to be used to obtain an escape time of 20 s. Thedifference in the escape times suggests that there is relativelyrapid divergence in the transduction pathways leading from phytochromeactivation (only one molecular species of phytochrome is foundin Mougeotia) to each of the two responses in the same cellularsystem. Because channel activation occurs 24 min afterirradiation while the escape time is 20 s, it is unlikely thatphytochrome acts directly on the channel. (Received September 26, 1995; Accepted December 28, 1995) 相似文献