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31.
Six xylariaceous fungi, including two Hypoxylon taxa and four Nemania taxa, are described as new. They were collected from either Costa Rica or Taiwan. Two of the Nemania species--N. flavitextura and N. primolutea--were cultured and typical Geniculosporium anamorphs were produced. 相似文献
32.
Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth 总被引:1,自引:0,他引:1
Porembka MR Mitchem JB Belt BA Hsieh CS Lee HM Herndon J Gillanders WE Linehan DC Goedegebuure P 《Cancer immunology, immunotherapy : CII》2012,61(9):1373-1385
Purpose
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immunosuppressive cells that are upregulated in cancer. Little is known about the prevalence and importance of MDSC in pancreas adenocarcinoma (PA).Experimental design
Peripheral blood, bone marrow, and tumor samples were collected from pancreatic cancer patients, analyzed for MDSC (CD15+CD11b+) by flow cytometry and compared to cancer-free controls. The suppressive capacity of MDSC (CD11b+Gr-1+) and the effectiveness of MDSC depletion were assessed in C57BL/6 mice inoculated with Pan02, a murine PA, and treated with placebo or zoledronic acid, a potent aminobisphosphonate previously shown to target MDSC. The tumor microenvironment was analyzed for MDSC (Gr1+CD11b+), effector T cells, and tumor cytokine levels.Results
Patients with PA demonstrated increased frequency of MDSC in the bone marrow and peripheral circulation which correlated with disease stage. Normal pancreas tissue showed no MDSC infiltrate, while human tumors avidly recruited MDSC. Murine tumors similarly recruited MDSC that suppressed CD8+ T cells in vitro and accelerated tumor growth in vivo. Treatment with zoledronic acid impaired intratumoral MDSC accumulation resulting in delayed tumor growth rate, prolonged median survival, and increased recruitment of T cells to the tumor. This was associated with a more robust type 1 response with increased levels of IFN-γ and decreased levels of IL-10.Conclusions
MDSC are important mediators of tumor-induced immunosuppression in pancreatic cancer. Inhibiting MDSC accumulation with zoledronic acid improves the host anti-tumor response in animal studies suggesting that efforts to block MDSC may represent a novel treatment strategy for pancreatic cancer. 相似文献33.
The non-homologous DNA end joining (NHEJ) pathway is a major double-strand DNA break repair pathway in cells of multicellular eukaryotes. Ku is a heterodimeric protein consisting of Ku70 and Ku86, and it is thought to be the first component to bind to a broken double-strand DNA end. Mice lacking Ku86 show features of premature aging, live about 6-12 months, and show a characteristic loss of neurons in the central nervous system during development. Cells from mice lacking Ku have increased numbers of chromosome breaks, a significant fraction of which are caused by oxidative metabolism. Overexpression of the cytoplasmic Cu/Zn superoxide dismutase (SOD1) from a transgene is known to increase the number of chromosome breaks in primary cells (presumably by increasing reactive oxygen species). Here we show that SOD1 overexpression in a Ku86-/- mouse results in embryonic lethality. This striking effect is, however, subject to a strain-specific modifier. Genome-wide marker analysis is most consistent with the modifier being on mouse chromosome 13. Analysis of 10 markers on chromosome 13 suggests that the modifier is within the same region as a modifier of the murine amyotropic lateral sclerosis (ALS) phenotype when it is caused by overexpression of a mutant form of SOD1. Based on these results, we propose a model in which oxidative metabolism causes chromosome breaks, leading to neuronal death; and this neuronal death may account for that seen in NHEJ mutant animals and in mammals with SOD1-mediated ALS. 相似文献
34.
When an γ‐irradiated Dy‐, Tm‐, Sm‐ or Mn‐doped CaSO4 crystal is impulsively deformed, two peaks appear in the ML intensity versus time curve, whereby the first ML peak is found in the deformation region and the second in the post‐deformation region of the crystals. In this study, intensities Im1 and Im2 corresponding to first and second ML peaks, respectively, increased linearly with an impact velocity v0 of the piston used to deform the crystals, and times tm1 and tm2 corresponding to the first and second ML peaks, respectively, decreased with impact velocity. Total ML intensity initially increased with impact velocity and then reached a saturation value for higher values of impact velocity. ML intensity increased with increasing γ‐doses and size of crystals. Results showed that the electric field produced as a result of charging of newly‐created surfaces caused tunneling of electrons to the valence band of the hole‐trapping centres. The free holes generated moved in the valence band and their subsequent recombination with electron trapping centres released energy, thereby resulting in excitation of luminescent centres. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
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36.
SARS-CoV M gene fragment was cloned and expressed as a recombinant protein fused with a V5 tag at the C-terminus in Vero E6
cells. In addition to un-glycosylated and glycosylated proteins, one product with smaller size initiated in-frame from the
third Met residues probably through ribosomal re-initiation was also detected. Translation initiated in-frame from the third
Met is unusual since the sequence around the first Met of SARS-CoV M protein contains the optimal consensus Kozak sequence.
The function of this smaller translated product awaits further investigation. Similar to other N-glycosylated proteins, glycosylation
of SARS-CoV M protein was occurred co-translationally in the presence of microsomes. The SARS-CoV M protein is predicted as
a triple-spanning membrane protein lack of a conventional signal peptide. The second and third trans-membrane regions (a.a.
46–68 and 78–100) are predicted to be the primary type helices, which will be able to penetrate into membrane by themselves,
while the first trans-membrane region (a.a. 14–36) is predicted to be the secondary type helix, which is considered to be
stabilized by the interaction with other trans-membrane segments. As expected, the second and third trans-membrane regions
were able to insert a cytoplasmic protein into the endoplasmic reticulum membrane more efficiently than the first one. These
results should be important for the study of SARS-CoV morphogenesis.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
37.
38.
Jian-Zhi Huang Ting-Chi Cheng Pei-Jung Wen Ming-Hsiun Hsieh Fure-Chyi Chen 《Plant cell reports》2009,28(10):1475-1486
Two pathways are used by higher plants for the biosynthesis of isoprenoid precursors: the mevalonate pathway in the cytosol
and a 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway in the plastids, with 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase (HDR) catalyzing the last step in the MEP pathway. In order to understand the contribution
of MEP pathway in isoprenoid biosynthesis of Oncidium orchid, a full-length cDNA corresponding to HDR from the flower tissues of Oncidium Gower Ramsey was cloned. The deduced OncHDR amino acid sequence contains a plastid signal peptide at the N-terminus and four
conserved cysteine residues. RT-PCR analysis of HDR in Oncidium flowering plants revealed ubiquitous expression in organs and tissues, with preferential expression in the floral organs.
Phylogenetic analysis revealed evolutionary conservation of the encoding HDR protein sequence. The genomic sequence of the
HDR in Oncidium is similar to that in Arabidopsis, grape, and rice in structure. Successful complementation by OncHDR of an E. coli hdr
−
mutant confirmed its function. Transgenic tobacco carrying the OncHDR promoter-GUS gene fusion showed expression in most tissues, as well as in reproductive organs, as revealed by histochemical staining.
Light induced strong GUS expression driven by the OncHDR promoter in transgenic tobacco seedlings. Taken together, our data suggest a role for OncHDR as a light-activated gene. 相似文献
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