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991.
We previously showed that bone marrow stem cells participate in the tumor vessel expansion that supports the growth of Ewing's sarcoma tumors in vivo. The purpose of this study was to determine the relative importance of two isoforms of vascular endothelial growth factor (VEGF) in tumor vessel expansion and recruitment of bone marrow-derived cells during tumor growth. We injected VEGF(165)-siRNA-transfected cells (TCsi/7-1), control siRNA-transfected cells (TC/si-control), or TC71 parental Ewing's sarcoma cells into nude mice. The TCsi/7-1 tumors were then treated with adenoviral vectors expressing VEGF(165) (Ad-VEGF(165)), VEGF(189) (Ad-VEGF(189)), or beta-galactosidase (Ad-beta-gal). Bone marrow cells labeled with fluorescent tracker dye were injected into the mice 3 weeks later. The TCsi/7-1 tumors were significantly smaller (P < 0.05), had decreased vessel density, and showed significantly lower bone marrow cell migration than did TC71 parental and TC/si-control tumors. Treatment with Ad-VEGF(165), but not Ad-VEGF(189) or Ad-beta-gal, resulted in a significant increase in bone marrow cell infiltration, tumor vessel density, and tumor growth. Immunohistochemical staining revealed that the injected bone marrow cells migrated to and incorporated into the expanding CD31(+) tumor vessel network. Taken together, these data show that VEGF(165) is a chemoattractant that recruits bone marrow cells into the tumor area. These data provide a mechanism by which Ewing's sarcoma cells induce vasculogenesis. 相似文献
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Koshkina NV Khanna C Mendoza A Guan H DeLauter L Kleinerman ES 《Molecular cancer research : MCR》2007,5(10):991-999
Low expression of Fas by different tumors including osteosarcoma, correlates with poor prognosis. We found that osteosarcoma lung metastases from patients expressed negligible amounts of Fas, but primary tumors often expressed high Fas levels. The reason for this discrepancy is unknown. We hypothesized that because FasL is constitutively expressed in the lungs, Fas-positive (Fas(+)) tumor cells entering the lungs would bind with FasL and die from Fas-induced apoptosis, resulting in the "selection" of Fas-negative (Fas(-)) cells, which would eventually form metastases. To test this hypothesis, we injected K7 osteosarcoma cells, which express functional Fas in vitro, into mice and confirmed that its bone tumors were Fas(+), but lung metastases were Fas(-). Next, to inhibit Fas signaling without affecting Fas expression, we transfected these cells with a FADD-dominant negative (FDN) plasmid and developed K7/FDN cells. Metastases formed by K7/FDN cells contained Fas(+) tumor cells. Moreover, K7/FDN cells were retained in the lungs longer and formed more lung metastases than K7 cells. In addition, the incidence of lung metastases in FasL-deficient mice injected with K7 cells was higher than that in wild-type mice. Metastases from FasL-deficient mice but not from wild-type mice contained Fas(+) tumor cells. Based on that, we conclude that Fas(-) osteosarcoma cells are selected during lung metastases formation and that inhibition of Fas signaling in tumors or lack of FasL in the host environment allows the proliferation of Fas(+) osteosarcoma cells in the lungs and promotes metastases growth. Therefore, Fas may be considered as a new therapeutic target for osteosarcoma treatment. 相似文献
993.
Intermolecular failure of L-type Ca2+ channel and ryanodine receptor signaling in hypertrophy 下载免费PDF全文
Xu M Zhou P Xu SM Liu Y Feng X Bai SH Bai Y Hao XM Han Q Zhang Y Wang SQ 《PLoS biology》2007,5(2):e21
Pressure overload–induced hypertrophy is a key step leading to heart failure. The Ca2+-induced Ca2+ release (CICR) process that governs cardiac contractility is defective in hypertrophy/heart failure, but the molecular mechanisms remain elusive. To examine the intermolecular aspects of CICR during hypertrophy, we utilized loose-patch confocal imaging to visualize the signaling between a single L-type Ca2+ channel (LCC) and ryanodine receptors (RyRs) in aortic stenosis rat models of compensated (CHT) and decompensated (DHT) hypertrophy. We found that the LCC-RyR intermolecular coupling showed a 49% prolongation in coupling latency, a 47% decrease in chance of hit, and a 72% increase in chance of miss in DHT, demonstrating a state of “intermolecular failure.” Unexpectedly, these modifications also occurred robustly in CHT due at least partially to decreased expression of junctophilin, indicating that intermolecular failure occurs prior to cellular manifestations. As a result, cell-wide Ca2+ release, visualized as “Ca2+ spikes,” became desynchronized, which contrasted sharply with unaltered spike integrals and whole-cell Ca2+ transients in CHT. These data suggested that, within a certain limit, termed the “stability margin,” mild intermolecular failure does not damage the cellular integrity of excitation-contraction coupling. Only when the modification steps beyond the stability margin does global failure occur. The discovery of “hidden” intermolecular failure in CHT has important clinical implications. 相似文献
994.
Drug and gene delivery using gold nanoparticles 总被引:2,自引:0,他引:2
Monolayer-functionalized gold nanoparticles provide attractive vehicles for pharmaceutical delivery applications as a result
of their size and the unique properties and release mechanisms imparted by their monolayer. This review provides examples
of recent advances in the field of drug and gene delivery using gold nanoparticles. 相似文献
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Guojing Shen Wei Hu Xianmeng Wang Xiangchun Zhou Zhongming Han Ahmed Sherif Mohammed Ayaad Yongzhong Xing 《植物学报(英文版)》2022,64(3):688-701
In the past, rice hybrids with strong heterosis have been obtained empirically, by developing and testing thousands of combinations. Here, we aimed to determine whether heterosis of an elite hybrid could be achieved by manipulating major quantitative trait loci. We used 202 chromosome segment substitution lines from the elite hybrid Shanyou 63 to evaluate single segment heterosis (SSH) of yield per plant and identify heterotic loci. All nine detected heterotic loci acted in a dominant fashion, and no SSH exhibited overdominance. Functional alleles of key yield-related genes Ghd7, Ghd7.1, Hd1, and GS3 were dispersed in both parents. No functional alleles of three investigated genes were expressed at higher levels in the hybrids than in the more desirable parents. A hybrid pyramiding eight heterotic loci in the female parent Zhenshan 97 background had a comparable yield to Shanyou 63 and much higher yield than Zhenshan 97. Five hybrids pyramiding eight or nine heterotic loci in the combined parental genome background showed similar yield performance to that of Shanyou 63. These results suggest that dominance underlying functional complementation is an important contributor to yield heterosis and that heterosis assembly might be successfully promised by manipulating several major dominant heterotic loci. 相似文献