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Berggren PO Yang SN Murakami M Efanov AM Uhles S Köhler M Moede T Fernström A Appelskog IB Aspinwall CA Zaitsev SV Larsson O de Vargas LM Fecher-Trost C Weissgerber P Ludwig A Leibiger B Juntti-Berggren L Barker CJ Gromada J Freichel M Leibiger IB Flockerzi V 《Cell》2004,119(2):273-284
An oscillatory increase in pancreatic beta cell cytoplasmic free Ca2+ concentration, [Ca2+]i, is a key feature in glucose-induced insulin release. The role of the voltage-gated Ca2+ channel beta3 subunit in the molecular regulation of these [Ca2+]i oscillations has now been clarified by using beta3 subunit-deficient beta cells. beta3 knockout mice showed a more efficient glucose homeostasis compared to wild-type mice due to increased glucose-stimulated insulin secretion. This resulted from an increased glucose-induced [Ca2+]i oscillation frequency in beta cells lacking the beta3 subunit, an effect accounted for by enhanced formation of inositol 1,4,5-trisphosphate (InsP3) and increased Ca2+ mobilization from intracellular stores. Hence, the beta3 subunit negatively modulated InsP3-induced Ca2+ release, which is not paralleled by any effect on the voltage-gated L type Ca2+ channel. Since the increase in insulin release was manifested only at high glucose concentrations, blocking the beta3 subunit in the beta cell may constitute the basis for a novel diabetes therapy. 相似文献
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Grote R Li L Tamaoka J Kato C Horikoshi K Antranikian G 《Extremophiles : life under extreme conditions》1999,3(1):55-62
A novel coccoid-shaped, hyperthermophilic, anaerobic archaeon, strain RG-20, was isolated from a deep-sea hydrothermal vent
fluid sample taken at 1394-m depth at the Mid-Okinawa Trough (27°32.7′N, 126°58.5′E). Cells of this isolate occur singly or
in pairs and are about 0.8 to 2 μm in diameter. Growth was observed at temperatures between 50° and 93°C, with an optimum
at 85°C. The pH range for growth is 5.0–9.0, with an optimum around 7.0. Strain RG-20 requires 1%–4% of NaCl for growth, and
cell lysis occurs at concentrations below 1%. The newly isolated strain grows preferentially in the presence of elemental
sulfur on proteinaceous substrates such as yeast extract, peptone, or tryptone, and no growth was observed on carbohydrates,
carboxylic acids, alcohols, or lipids. This microorganism is resistant to streptomycin, chloramphenicol, ampicillin, and kanamycin
at concentrations up to 150 μg/ml, but is susceptible to rifampicin. Analysis of the hydrolyzed core lipids by thin-layer
chromatography (TLC) revealed the presence of archaeol and caldarchaeol. The mol% G+C content of the DNA is 55.8. Partial
sequencing of the 16S rDNA indicates that strain RG-20 belongs to the genus Thermococcus. Considering these data and on the basis of the results from DNA-DNA hybridization studies, we propose that this strain should
be classified as a new species named Thermococcus siculi (si′cu.li. L. gen. n. siculi, of the deep-sea [siculum, deep-sea in literature of Ovid], referring to the location of the sample site, a deep-sea hydrothermal vent). The type strain
is isolate RG-20 (DSM No. 12349).
Received: May 11, 1998 / Accepted: July 24, 1998 相似文献
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Jingbo Wang Xinmin Zhou Lina Cui Li Yan Jie Liang Xin Cheng Lijuan Qiao Yongquan Shi Zheyi Han Yunxin Cao Ying Han Daiming Fan 《Cytotherapy》2010,12(8):1022-1034
Background aimsCirculating monocytes have been exploited as an important progenitor cell resource for hepatocytes in vitro and are instrumental in the removal of fibrosis. We investigated the significance of monocytes in peripheral blood stem cells (PBSC) for the treatment of liver cirrhosis.MethodsRat CD14+ monocytes in PBSC were mobilized with granulocyte-colony-stimulating factor (G-CSF) and harvested by magnetic cell sorting (MACS). Female rats with carbon tetrachloride (CCl4)-induced liver cirrhosis were injected CM-DiI-labeled monocytes, CD14? cells (1 × 107 cells/rat) or saline via the portal vein.ResultsRat CD14+ and CD11b+ monocytes in PBSC were partly positive for CD34, CD45, CD44, Oct3/4 and Sox2, suggesting monocytes with progenitor capacity. Compared with CD14? cell-infused and saline-injected rats, rats undergoing monocyte transplantation showed a gradually increased serum albumin level and decreased portal vein pressure, resulting in a significantly improved survival rate. Meanwhile, monocyte transplantation apparently attenuated liver fibrosis by analysis for fibronectin, α2-(1)-procollagen, α-smooth muscle aorta (SMA) and transforming growth factor (TGF)-β. Transplanted monocytes mainly clustered in periportal areas of liver, in which 1.8% cells expressed hepatocyte marker albumin and CK18. The expression level of hepatocyte growth factor (HGF), TGF-α, extracellular matrix (EGF) and vascular endothelial growth factor (VEGF) increased, while monocyte transplantation enhanced hepatocyte proliferation. On the other hand, the activities and expression of matrix metalloproteinases (MMP) increased while tissue inhibitor of metalloproteinase (TIMP)-1 expression significantly reduced in monocyte-transplanted livers. Some transplanted monocytes expressed MMP-9 and -13.ConclusionsThe data suggest that CD14+ monocytes in PBSC contribute to hepatocyte regeneration and extracellular matrix (ECM) remodeling in rat liver cirrhosis much more than CD14? cells, and might offer a therapeutic alternative for patients with liver cirrhosis. 相似文献
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Liwen Liang Huili Li Ting Cao Lina Qu Lulu Zhang Guo-Chang Fan Peter A. Greer Jianmin Li Douglas L. Jones Tianqing Peng 《The Journal of biological chemistry》2020,295(49):16840
The human cardiovascular system has adapted to function optimally in Earth''s 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities. 相似文献
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Nitrogen-doped carbon dots (NCDs) with bright blue fluorescence were constructed by a hydrothermal method using sucrose and l- proline as raw materials. The NCDs were characterized by transmitted electron microscopy, X-ray diffraction, Fourier-transform infrared spectrometry, X-ray photoelectron spectroscopy, and ultraviolet-visible absorption and fluorescence spectroscopy to investigate the morphology, elemental composition, and optical properties. The NCDs had good water solubility, high dispersibility with an average diameter of only 1.7 nm, and satisfactory optical properties with a fluorescence quantum yield of 23.4%. The NCDs were employed for the detection of bilirubin. A good linear response of the NCDs in the range 0.35–9.78 μM was obtained for bilirubin with a detection limit of 33 nM. The NCDs were also applied to the analysis of real samples, serum and urine, with a recovery of 95.34% to 104.66%. The low cytotoxicity and good biocompatibility of the NCDs were indicated by an MTT assay and cell imaging of HeLa cells. Compared with other detection systems, using NCDs for bilirubin detection was a facile and efficient method with good selectivity and sensitivity. 相似文献
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[目的] 研究核桃壳提取液(walnut shell extracts,WSE)对单针藻Monoraphidium sp.QLZ-3生长和油脂积累的影响。[方法] 向BG-11培养基中添加不同量的WSE(培养基中保留有BG-11中全部营养成分)。[结果] 结果显示,当BG-11培养基中的WSE含量为40%时,单针藻的生物量产率及油脂产率达到(534.70±4.07)mg/(L·d)和(296.35±15.36)mg/(L·d),相比对照组分别提高了的14.82%和33.50%,蛋白质和碳水化合物含量分别有不同程度的上调和下调。与对照组相比,微藻中谷胱甘肽(glutathione,GSH)和超氧化物歧化酶(superoxide dismutase,SOD)含量与活性均上调。此外,WSE作用下,微藻对多酚的移除达到84.37%,同时上调了核酮糖1,5-二磷酸羧化酶基因(ribulose 1,5-bisphosphate carboxylase/oxygenase,rbcL)和乙酰辅酶A羧化酶(acetyl coenzyme A carboxylase,accD)基因的表达量。[结论] 研究表明,WSE联合BG-11可以提高微藻的生物量产率和油脂产率,降低微藻培养的原料成本,为核桃壳的资源化利用及微藻的工业化生产提供了一定的技术支撑。 相似文献
50.
Harnessing the knowledge we have gained on the cell cycle disruption caused by human papillomaviruses (HPV) will likely lead to improved screening modalities for cervical cancer and its precursors. An easily applied biomarker that has high specificity and sensitivity would represent an attractive alternative or complement to cytology and HPV testing. To date, a number of promising markers have been investigated. These include p16(INK4A), MIB-1, BD-ProEx C, and L1. Newer possibilities involve a variety of gene products associated with aberrations of chromosome 3q, such as telomerase, p63, and PIK3CA, as well the combination of biomarkers such as p16(INK4A) and MIB-1 in the same assay. Although none of them has yet been incorporated into screening algorithms or found its way into routine practice, their performance characteristics remain a focus of current investigations. This review summarizes what we know and where we hope to go in translating basic pathobiology into clinical practice. 相似文献