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61.
RueiLung Lin Hilaree N. Frazier Katie L. Anderson Sami L. Case Adam O. Ghoweri Olivier Thibault 《Aging cell》2022,21(7)
Neuronal hippocampal Ca2+ dysregulation is a critical component of cognitive decline in brain aging and Alzheimer''s disease and is suggested to impact communication and excitability through the activation of a larger after hyperpolarization. However, few studies have tested for the presence of Ca2+ dysregulation in vivo, how it manifests, and whether it impacts network function across hundreds of neurons. Here, we tested for neuronal Ca2+ network dysregulation in vivo in the primary somatosensory cortex (S1) of anesthetized young and aged male Fisher 344 rats using single‐cell resolution techniques. Because S1 is involved in sensory discrimination and proprioception, we tested for alterations in ambulatory performance in the aged animal and investigated two potential pathways underlying these central aging‐ and Ca2+‐dependent changes. Compared to young, aged animals displayed increased overall activity and connectivity of the network as well as decreased ambulatory speed. In aged animals, intranasal insulin (INI) increased network synchronicity and ambulatory speed. Importantly, in young animals, delivery of the L‐type voltage‐gated Ca2+ channel modifier Bay‐K 8644 altered network properties, replicating some of the changes seen in the older animal. These results suggest that hippocampal Ca2+ dysregulation may be generalizable to other areas, such as S1, and might engage modalities that are associated with locomotor stability and motivation to ambulate. Further, given the safety profile of INI in the clinic and the evidence presented here showing that this central dysregulation is sensitive to insulin, we suggest that these processes can be targeted to potentially increase motivation and coordination while also reducing fall frequency with age. 相似文献
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63.
J. Jansen M. Fedecostante M.J. Wilmer L.P. van den Heuvel J.G. Hoenderop R. Masereeuw 《Biotechnology advances》2014
With the world-wide increase of patients with renal failure, the development of functional renal replacement therapies have gained significant interest and novel technologies are rapidly evolving. Currently used renal replacement therapies insufficiently remove accumulating waste products, resulting in the uremic syndrome. A more preferred treatment option is kidney transplantation, but the shortage of donor organs and the increasing number of patients waiting for a transplant warrant the development of novel technologies. The bioartificial kidney (BAK) is such promising biotechnological approach to replace essential renal functions together with the active secretion of waste products. The development of the BAK requires a multidisciplinary approach and evolves at the intersection of regenerative medicine and renal replacement therapy. Here we provide a concise review embracing a compact historical overview of bioartificial kidney development and highlighting the current state-of-the-art, including implementation of living-membranes and the relevance of extracellular matrices. We focus further on the choice of relevant renal epithelial cell lines versus the use of stem cells and co-cultures that need to be implemented in a suitable device. Moreover, the future of the BAK in regenerative nephrology is discussed. 相似文献
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Summary Two sugarbeet (Beta vulgaris L.) genotypes, REL-1 and REL-2, were used to measure the level of somatic embryo and shoot production from hormone-autonomous
callus plated under varied nutrient medium combinations of abscisic acid with the growth regulators 6-benzyladenine, 1-naphthaleneacetic
acid, or 2,4-dichlorophenoxyacetic acid, with eight sole nitrogen sources, or with different sucrose concentrations. Clone
REL-2 produced embryos up to 35-fold more frequently than clone REL-1. Inclusion of abscisic acid at some concentrations consistently
improved embryo production in all experiments and was observed to stimulate shoot production. At some concentrations, 1-naphthaleneacetic
acid as well as urea and glutamine stimulated greater embryo production over the control, but only for REL-1, for which there
was greater room for improvement. Three and five percent sucrose were superior to 1, 7, and 9%. Higher initial 6-benzyladenine
concentration [in the range 0, 0.1−1.0 mg/L (0.44−4.44 μM)] was associated with lower embryo production but greater shoot regeneration for both clones. REL-2 was significantly better
than REL-1 in shoot regeneration. The range of embryo production was more than 35-fold between genotypes, whereas the range
of physiological effects was no greater than 10-fold. REL-2 has been released to sugarbeet researchers because of its superior
embryogenic and shoot regeneration abilities for application in biotechnology. 相似文献
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本研究采用活性追踪的方法,逐步从人工培养蝉花虫草分离获得A(50%乙醇回流提取)、B(膜分离)、C(大孔树脂洗脱)和D(Sephadex LH20柱纯化)等4种样品,单一化合物D纯度为98.62%,鉴定为N6‐(2‐羟乙基)腺苷[N6‐(2‐hydroxyethyl)‐adenosine,HEA]。研究各样品对戊四唑(pentylenetetrazol,PTZ)诱导的小鼠惊厥模型的影响,以及选择性腺苷A1受体(AA1R)拮抗剂DPCPX或选择性腺苷A2A受体(AA2AR)拮抗剂ZM241385对HEA作用的影响,并采用苏木精-伊红(hematoxylin-eosin,HE)染色、免疫组化(immunohistochemical,IHC)染色和蛋白质免疫印迹(Western blot,WB)等技术进一步探究HEA抗惊厥作用的机制。结果表明,各样品(i.p.)均有抗惊厥活性,HEA(40–60mg/kg,i.p.)能显著延长惊厥小鼠的存活时间和降低死亡率,DPCPX(2mg/kg,i.p.)能够拮抗HEA的抗惊厥作用,而ZM241385无此作用;HE、IHC和WB的结果进一步揭示DPCPX显著降低HEA的作用。综上所述,蝉花虫草的HEA具有抗惊厥作用,并且可能通过激活腺苷A1受体而起作用。 相似文献
68.
Lentiviral vectors have been used for gene transfer into the liver but their ability to efficiently transduce quiescent hepatocytes
remains controversial. Lentivirus-mediated gene transfer is more efficient in cycling cells. We determine the effect of H-IL6
in the lentiviral transduction. The lentiviral vector was used to transduce HepG2 cells and mice liver cells, previously treated
with H-IL6. The highest transduction level was observed in HepG2 cells treated with 30 ng/mL H-IL6 and in the mice that received
4 μg H-IL6. Our results suggest that H-IL6 is an inducer of lentiviral gene transfer into the liver cells without any toxicity. 相似文献
69.
70.
Lin CT Tsai YC He L Calizo R Chou HH Chang TC Soong YK Hung CF Lai CH 《Journal of biomedical science》2006,13(4):481-488
Summary The HPV oncoproteins E6 and E7 are consistently expressed in HPV-associated cancer cells and are responsible for their malignant transformation. Therefore, HPV E6 and E7 are ideal target antigens for developing vaccines and immunotherapeutic strategies against HPV-associated neoplasms. Recently, it has been demonstrated that codon optimization of the HPV-16 E7 gene resulted in highly efficient translation of E7 and increased the immunogenicity of E7-specific DNA vaccines. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a codon-optimized HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) and characterized the E6-specific CD8+ T cell immune responses as well as the protective and therapeutic anti-tumor effects in vaccinated C57BL/6 mice. Our data indicated that transfection of human embryonic kidney cells (293 cells) with pNGVL4a-E6/opt resulted in highly efficient translation of E6. In addition, vaccination with pNGVL4a-E6/opt significantly enhanced E6-specific CD8+ T cell immune responses in C57BL/6 mice. Mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and therapeutic antitumor effects against challenge with E6-expressing tumor cell line, TC-1. Thus, DNA vaccines encoding a codon-optimized HPV-16 E6 may be a promising strategy for improving the potency of prophylactic and therapeutic HPV vaccines with potential clinical implications. 相似文献