全文获取类型
收费全文 | 7343篇 |
免费 | 563篇 |
国内免费 | 3篇 |
专业分类
7909篇 |
出版年
2023年 | 29篇 |
2022年 | 60篇 |
2021年 | 119篇 |
2020年 | 75篇 |
2019年 | 71篇 |
2018年 | 115篇 |
2017年 | 92篇 |
2016年 | 171篇 |
2015年 | 277篇 |
2014年 | 338篇 |
2013年 | 472篇 |
2012年 | 583篇 |
2011年 | 556篇 |
2010年 | 363篇 |
2009年 | 345篇 |
2008年 | 446篇 |
2007年 | 480篇 |
2006年 | 483篇 |
2005年 | 464篇 |
2004年 | 415篇 |
2003年 | 450篇 |
2002年 | 424篇 |
2001年 | 83篇 |
2000年 | 62篇 |
1999年 | 74篇 |
1998年 | 84篇 |
1997年 | 62篇 |
1996年 | 66篇 |
1995年 | 54篇 |
1994年 | 52篇 |
1993年 | 46篇 |
1992年 | 48篇 |
1991年 | 34篇 |
1990年 | 31篇 |
1989年 | 27篇 |
1988年 | 17篇 |
1987年 | 20篇 |
1986年 | 23篇 |
1985年 | 31篇 |
1984年 | 25篇 |
1983年 | 22篇 |
1982年 | 20篇 |
1981年 | 16篇 |
1980年 | 12篇 |
1979年 | 16篇 |
1977年 | 13篇 |
1976年 | 12篇 |
1974年 | 13篇 |
1973年 | 18篇 |
1969年 | 13篇 |
排序方式: 共有7909条查询结果,搜索用时 15 毫秒
111.
Acceleration of cyanobacterial dominance in north temperate‐subarctic lakes during the Anthropocene 下载免费PDF全文
Zofia E. Taranu Irene Gregory‐Eaves Peter R. Leavitt Lynda Bunting Teresa Buchaca Jordi Catalan Isabelle Domaizon Piero Guilizzoni Andrea Lami Suzanne McGowan Heather Moorhouse Giuseppe Morabito Frances R. Pick Mark A. Stevenson Patrick L. Thompson Rolf D. Vinebrooke 《Ecology letters》2015,18(4):375-384
Increases in atmospheric temperature and nutrients from land are thought to be promoting the expansion of harmful cyanobacteria in lakes worldwide, yet to date there has been no quantitative synthesis of long‐term trends. To test whether cyanobacteria have increased in abundance over the past ~ 200 years and evaluate the relative influence of potential causal mechanisms, we synthesised 108 highly resolved sedimentary time series and 18 decadal‐scale monitoring records from north temperate‐subarctic lakes. We demonstrate that: (1) cyanobacteria have increased significantly since c. 1800 ce , (2) they have increased disproportionately relative to other phytoplankton, and (3) cyanobacteria increased more rapidly post c. 1945 ce . Variation among lakes in the rates of increase was explained best by nutrient concentration (phosphorus and nitrogen), and temperature was of secondary importance. Although cyanobacterial biomass has declined in some managed lakes with reduced nutrient influx, the larger spatio‐temporal scale of sedimentary records show continued increases in cyanobacteria throughout the north temperate‐subarctic regions. 相似文献
112.
Wolowczuk I Hennart B Leloire A Bessede A Soichot M Taront S Caiazzo R Raverdy V Pigeyre M;ABOS Consortium Guillemin GJ Allorge D Pattou F Froguel P Poulain-Godefroy O 《American journal of physiology. Regulatory, integrative and comparative physiology》2012,303(2):R135-R143
Human obesity is characterized by chronic low-grade inflammation in white adipose tissue and is often associated with hypertension. The potential induction of indoleamine 2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme in tryptophan/kynurenine degradation pathway, by proinflammatory cytokines, could be associated with these disorders but has remained unexplored in obesity. Using immunohistochemistry, we detected IDO1 expression in white adipose tissue of obese patients, and we focused on its contribution in the regulation of vascular tone and on its immunoregulatory effects. Concentrations of tryptophan and kynurenine were measured in sera of 36 obese and 15 lean women. The expression of IDO1 in corresponding omental and subcutaneous adipose tissues and liver was evaluated. Proinflammatory markers and T-cell subsets were analyzed in adipose tissue via the expression of CD14, IL-18, CD68, TNFα, CD3ε, FOXP3 [a regulatory T-cell (Treg) marker] and RORC (a Th17 marker). In obese subjects, the ratio of kynurenine to tryptophan, which reflects IDO1 activation, is higher than in lean subjects. Furthermore, IDO1 expression in both adipose tissues and liver is increased and is inversely correlated with arterial blood pressure. Inflammation is associated with a T-cell infiltration in obese adipose tissue, with predominance of Th17 in the omental compartment and of Treg in the subcutaneous depot. The Th17/Treg balance is decreased in subcutaneous fat and correlates with IDO1 activation. In contrast, in the omental compartment, despite IDO1 activation, the Th17/Treg balance control is impaired. Taken together, our results suggest that IDO1 activation represents a local compensatory mechanism to limit obesity-induced inflammation and hypertension. 相似文献
113.
Eric J. Hartman Beejan Asady Julia D. Romano Isabelle Coppens 《Molecular biology of the cell》2022,33(5)
After mammalian cell invasion, the parasite Toxoplasma multiplies in a self-made membrane-bound compartment, the parasitophorous vacuole (PV). We previously showed that Toxoplasma interacts with many host cell organelles, especially from recycling pathways, and sequestrates Rab11A and Rab11B vesicles into the PV. Here, we examine the specificity of host Rab11 vesicle interaction with the PV by focusing on the recruitment of subpopulations of Rab11 vesicles characterized by different effectors, for example, Rab11-family interacting roteins (FIPs) or Arf6. Our quantitative microscopic analysis illustrates the presence of intra-PV vesicles with FIPs from class I (FIP1C, FIP2, FIP5) and class II (FIP3, FIP4) but to various degrees. The intra-PV delivery of vesicles with class I, but not class II, FIPs is dependent on Rab11 binding. Cell depletion of Rab11A results in a significant decrease in intra-PV FIP5, but not FIP3 vesicles. Class II FIPs also bind to Arf6, and we observe vesicles associated with FIP3-Rab11A or FIP3-Arf6 complexes concomitantly within the PV. Abolishing FIP3 binding to both Rab11 and Arf6 reduces the number of intra-PV FIP3 vesicles. These data point to a selective process of mammalian Rab11 vesicle recognition and scavenging mediated by Toxoplasma, suggesting that specific parasite PV proteins may be involved in these processes. 相似文献
114.
Sophie Sluysmans Andrea Salmaso Florian Rouaud Isabelle Man Marisa Brini Sandra Citi 《The Journal of biological chemistry》2022,298(8)
The plasma membrane calcium ATPase (PMCA) extrudes calcium from the cytosol to the extracellular space to terminate calcium-dependent signaling. Although the distribution of PMCA is crucial for its function, the molecular mechanisms that regulate the localization of PMCA isoforms are not well understood. PLEKHA7 is implicated by genetic studies in hypertension and the regulation of calcium handling. PLEKHA7 recruits the small adapter protein PDZD11 to adherens junctions, and together they control the trafficking and localization of plasma membrane associated proteins, including the Menkes copper ATPase. Since PDZD11 binds to the C-terminal domain of b-isoforms of PMCA, PDZD11 and its interactor PLEKHA7 could control the localization and activity of PMCA. Here, we test this hypothesis using cultured cell model systems. We show using immunofluorescence microscopy and a surface biotinylation assay that KO of either PLEKHA7 or PDZD11 in mouse kidney collecting duct epithelial cells results in increased accumulation of endogenous PMCA at lateral cell–cell contacts and PDZ-dependent ectopic apical localization of exogenous PMCA4x/b isoform. In HeLa cells, coexpression of PDZD11 reduces membrane accumulation of overexpressed PMCA4x/b, and analysis of cytosolic calcium transients shows that PDZD11 counteracts calcium extrusion activity of overexpressed PMCA4x/b, but not PMCA4x/a, which lacks the PDZ-binding motif. Moreover, KO of PDZD11 in either endothelial (bEnd.3) or epithelial (mouse kidney collecting duct) cells increases the rate of calcium extrusion. Collectively, these results suggest that the PLEKHA7–PDZD11 complex modulates calcium homeostasis by regulating the localization of PMCA. 相似文献
115.
116.
Juliana A. Silva Ana Isabelle Pinheiro Maria Luiza Dourado Lilian Medina Adriano Queiroz Luiz Henrique Guimares Marcus Miranda Lessa Ednaldo L. Lago Paulo Roberto L. Machado Mary E. Wilson Edgar M. Carvalho Albert Schriefer 《PLoS neglected tropical diseases》2022,16(6)
BackgroundLeishmaniases are neglected tropical diseases that inflict great burden to poor areas of the globe. Intense research has aimed to identify parasite genetic signatures predictive of infection outcomes. Consistency of diagnostic tools based on these markers would greatly benefit from accurate understanding of Leishmania spp. population genetics. We explored two chromosomal loci to characterize a population of L. braziliensis causing human disease in Northeast Brazil.Methodology/Principal findingsTwo temporally distinct samples of L. braziliensis were obtained from patients attending the leishmaniasis clinic at the village of Corte de Pedra: (2008–2011) primary sample, N = 120; (1999–2001) validation sample, N = 35. Parasites were genotyped by Sanger’s sequencing of two 600 base pairs loci starting at nucleotide positions 3,074 and 425,451 of chromosomes 24 and 28, respectively. Genotypes based on haplotypes of biallelic positions in each locus were tested for several population genetic parameters as well as for geographic clustering within the region. Ample geographic overlap of genotypes at the two loci was observed as indicated by non-significant Cusick and Edward’s comparisons. No linkage disequilibrium was detected among combinations of haplotypes for both parasite samples. Homozygous and heterozygous genotypes displayed Hardy-Weinberg equilibrium (HWE) at both loci in the two samples when straight observed and expected counts were compared by Chi-square (p>0.5). However, Bayesian statistics using one million Monte-Carlo randomizations disclosed a less robust HWE for chromosome 24 genotypes, particularly in the primary sample (p = 0.04). Fixation indices (Fst) were consistently lower than 0.05 among individuals of the two samples at both tested loci, and no intra-populational structuralization could be detected using STRUCTURE software.Conclusions/SignificanceThese findings suggest that L. braziliensis can maintain stable populations in foci of human leishmaniasis and are capable of robust genetic recombination possibly due to events of sexual reproduction during the parasite’s lifecycle. 相似文献
117.
118.
119.
120.
Beuneu H Deguine J Bouvier I Di Santo JP Albert ML Bousso P 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(5):2084-2088
NK cells are cytotoxic lymphocytes that are most efficient at fulfilling their functions after a phase of priming provided by cytokines and/or accessory cells. Although type I IFNs are known to be important in this process, it remains unclear whether they act directly on NK cells or indirectly on accessory cells. We used adoptive transfer experiments and mixed bone marrow chimeras to dissect the requirement for type I IFN signaling in response to the dsRNA analog polyinosinic-polycytidylic acid. We demonstrate that optimal NK cell priming requires type I IFNs to signal on both NK cells and accessory cells. In the absence of IL-15, the residual NK cell activation was strictly dependent on cell-intrinsic IFNAR signaling in NK cells. Our results suggest that type I IFNs produced following viral infection simultaneously target accessory cells for IL-15 transpresentation and NK cells themselves and that these two pathways cooperate for NK cell priming. 相似文献