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21.
Iron is essential for the survival as well as the proliferation and maturation of developing erythroid precursors (EP) into hemoglobin-containing red blood cells. The transferrin-transferrin receptor pathway is the main route for erythroid iron uptake. Using a two-phase culture system, we have previously shown that placental ferritin as well as macrophages derived from peripheral blood monocytes could partially replace transferrin and support EP growth in a transferrin-free medium. We now demonstrate that in the absence of transferrin, ferritin synthesized and secreted by macrophages can serve as an iron source for EP. Macrophages trigger an increase in both the cytosolic and the mitochondrial labile iron pools, in heme and in hemoglobin synthesis, along with a decrease in surface transferrin receptors. Inhibiting macrophage exocytosis, binding extracellular ferritin with specific antibodies, inhibiting EP receptor-mediated endocytosis or acidification of EP lysosomes, all resulted in a decreased EP growth when co-cultured with macrophages under transferrin-free conditions. The results suggest that iron taken up by macrophages is incorporated mainly into their ferritin, which is subsequently secreted by exocytosis. Nearby EP are able to take up this ferritin probably through clathrin-dependent, receptor-mediated endocytosis into endosomes, which following acidification and proteolysis release the iron from the ferritin, making it available for regulatory and synthetic purposes. Thus, macrophages support EP development under transferrin-free conditions by delivering essential iron in the form of metabolizable ferritin. 相似文献
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Carlos Landa-Solís Julio Granados-Montiel Anell Olivos-Meza Carmina Ortega-Sánchez Mónica Cruz-Lemini Cecilia Hernández-Flores María Eugenia Chang-González Ricardo Gómez García Brenda Olivos-Díaz María Cristina Velasquillo-Martínez Carlos Pineda Clemente Ibarra 《Cell and tissue banking》2016,17(1):137-145
Mobilized peripheral blood (MPB) bone marrow cells possess the potential to differentiate into a variety of mesenchymal tissue types and offer a source of easy access for obtaining stem cells for the development of experimental models with applications in tissue engineering. In the present work, we aimed to isolate by magnetic activated cell sorting CD90+ cells from MPB by means of the administration of Granulocyte-Colony Stimulating Factor and to evaluate cell proliferation capacity, after thawing of the in vitro culture of this population of mesenchymal stem cells (MSCs) in sheep. We obtained a median of 8.2 ± 0.6 million of CD90+ cells from the 20-mL MPB sample. After thawing, at day 15 under in vitro culture, the mean CD90+ cells determined by flow cytometry was 92.92 ± 1.29 % and cell duplication time determined by crystal violet staining was 47.59 h. This study describes for the first time the isolation, characterization, and post-in vitro culture thawing of CD90+ MSCs from mobilized peripheral blood in sheep. This population can be considered as a source of MSCs for experimental models in tissue engineering research. 相似文献
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The first endocast of the extinct dodo (Raphus cucullatus) and an anatomical comparison amongst close relatives (Aves,Columbiformes) 下载免费PDF全文
Maria Eugenia Leone Gold Estelle Bourdon Mark A. Norell 《Zoological Journal of the Linnean Society》2016,177(4):950-963
The dodo (Raphus cucullatus) became extinct only 100 years after humans first arrived on the Indian Ocean island of Mauritius. Even though it has become an example of oddity, obsolescence, stupidity, and extinction, most aspects of its biology are still unknown. We used high‐resolution X‐ray computed tomography (CT) scanning to examine the endocranial morphology of the dodo and compare this virtual endocast to eight close relatives. Enlarged olfactory bulbs are a shared characteristic of the Raphinae and posteriorly angled semicircular canals are particular to the dodo compared with the other eight species sampled here. A regression of log endocranial volume against log body size shows that the dodo has an endocranial volume on par with other pigeons. Aspects of the dodo's biology are discussed in relation to these endocranial features. 相似文献
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A Lamana A Balsa B Rueda AM Ortiz L Nuño ME Miranda-Carus MF Gonzalez-Escribano MA Lopez-Nevot D Pascual-Salcedo J Martin I González-Álvaro 《PloS one》2012,7(8):e43661
Background
The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis.Methodology and Results
We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5′ allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01–0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = −0.27 [−0.56– −0.01], p = 0.042; TT genotype = −0.68 [−1.64– −0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype.Conclusions
Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability. 相似文献28.
H Attar K Bedard E Migliavacca M Gagnebin Y Dupré P Descombes C Borel S Deutsch H Prokisch T Meitinger D Mehta E Wichmann JM Delabar ET Dermitzakis KH Krause SE Antonarakis 《PloS one》2012,7(8):e43566
Natural variation in DNA sequence contributes to individual differences in quantitative traits. While multiple studies have shown genetic control over gene expression variation, few additional cellular traits have been investigated. Here, we investigated the natural variation of NADPH oxidase-dependent hydrogen peroxide (H2O2 release), which is the joint effect of reactive oxygen species (ROS) production, superoxide metabolism and degradation, and is related to a number of human disorders. We assessed the normal variation of H2O2 release in lymphoblastoid cell lines (LCL) in a family-based 3-generation cohort (CEPH-HapMap), and in 3 population-based cohorts (KORA, GenCord, HapMap). Substantial individual variation was observed, 45% of which were associated with heritability in the CEPH-HapMap cohort. We identified 2 genome-wide significant loci of Hsa12 and Hsa15 in genome-wide linkage analysis. Next, we performed genome-wide association study (GWAS) for the combined KORA-GenCord cohorts (n = 279) using enhanced marker resolution by imputation (>1.4 million SNPs). We found 5 significant associations (p<5.00×10−8) and 54 suggestive associations (p<1.00×10−5), one of which confirmed the linked region on Hsa15. To replicate our findings, we performed GWAS using 58 HapMap individuals and ∼2.1 million SNPs. We identified 40 genome-wide significant and 302 suggestive SNPs, and confirmed genome signals on Hsa1, Hsa12, and Hsa15. Genetic loci within 900 kb from the known candidate gene p67phox on Hsa1 were identified in GWAS in both cohorts. We did not find replication of SNPs across all cohorts, but replication within the same genomic region. Finally, a highly significant decrease in H2O2 release was observed in Down Syndrome (DS) individuals (p<2.88×10−12). Taken together, our results show strong evidence of genetic control of H2O2 in LCL of healthy and DS cohorts and suggest that cellular phenotypes, which themselves are also complex, may be used as proxies for dissection of complex disorders. 相似文献
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Leys, used for grazing or production of forage to be conserved as silage or hay, are very important crops in northern areas.
In order to measure the N2 fixation in leys of varying ages and during different parts of the season, detailed measurements were taken of yield, N2 fixation and the amounts of N remaining in the field after harvesting red clover (Trifolium pratense L.)-grass leys at a site in northern Sweden, where they are generally harvested twice per growing season. Entire plants,
including stubble and roots, were sampled at the time of first and second harvest and, in addition, at the end of the growing
season in three neighbouring fields, carrying a first, a second and a third year ley, respectively. N2 fixation was measured by both 15N isotope dilution (ID) and 15N natural abundance (NA) methods. The proportion of clover dry matter (DM) in the stands increased from the first to the second
harvest, but the grasses dominated throughout the entire season, especially below ground. The N concentrations, in both herbage
and whole plants, were about twice as high in the clover as in the grasses. Seasonal variations in N concentrations were minor,
and total N contents followed the same trends as DM. The clover acquired nearly all of its N from N2 fixation: the proportion of N in clover herbage derived from N2 fixation was often >0.8 throughout the season. The variations in the amounts of N2 fixed during the course of the season corresponded well to the seasonal changes in clover biomass. Amounts of fixed N2 allocated to clover herbage during the whole season were in the range 4 to 6 g N m−2 in this unusually rainy year. Calculations of daily N allocation rates to herbage showed that N uptake rates were similar,
and high, in grasses during May–June and July–August, while N2 fixation rates in clover were about 10-fold as high in July–August as in May–June, reflecting the need for N in clover growth.
The proportion of N remaining in clover stubble and roots after the first and second harvests was about 60 and 25%, respectively,
while about 60% of the N in grasses remained in stubble and roots after both harvests. The considerable amounts of biomass
and N that were left in field after harvesting red clover-grass leys are important for re-growth of the plants and provide
substantial N fertilization for the next crop in the crop rotation. 相似文献