全文获取类型
收费全文 | 42507篇 |
免费 | 3389篇 |
国内免费 | 2437篇 |
专业分类
48333篇 |
出版年
2024年 | 61篇 |
2023年 | 484篇 |
2022年 | 1137篇 |
2021年 | 1970篇 |
2020年 | 1223篇 |
2019年 | 1511篇 |
2018年 | 1418篇 |
2017年 | 1087篇 |
2016年 | 1636篇 |
2015年 | 2454篇 |
2014年 | 2883篇 |
2013年 | 3130篇 |
2012年 | 3637篇 |
2011年 | 3437篇 |
2010年 | 1972篇 |
2009年 | 1816篇 |
2008年 | 2133篇 |
2007年 | 1912篇 |
2006年 | 1643篇 |
2005年 | 1469篇 |
2004年 | 1232篇 |
2003年 | 1092篇 |
2002年 | 951篇 |
2001年 | 858篇 |
2000年 | 743篇 |
1999年 | 724篇 |
1998年 | 441篇 |
1997年 | 469篇 |
1996年 | 448篇 |
1995年 | 395篇 |
1994年 | 384篇 |
1993年 | 310篇 |
1992年 | 442篇 |
1991年 | 386篇 |
1990年 | 333篇 |
1989年 | 247篇 |
1988年 | 239篇 |
1987年 | 200篇 |
1986年 | 142篇 |
1985年 | 187篇 |
1984年 | 128篇 |
1983年 | 110篇 |
1982年 | 80篇 |
1981年 | 66篇 |
1980年 | 57篇 |
1979年 | 74篇 |
1978年 | 70篇 |
1977年 | 57篇 |
1976年 | 50篇 |
1973年 | 51篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Yanan Ma Shanshan Wang Yongle Wu Bihan Liu Lei Li Wenjing Wang Honglei Weng Huiguo Ding 《Cell death & disease》2022,13(3)
Hepatic stellate cells (HSC) and hydrogen sulfide (H2S) both play important roles in the development of hepatocellar carcinoma (HCC). Whereas, in the microenvironment of HCC, whether HSC participate in regulating the biological process of HCC cells by releasing H2S remains elusive. In vitro, Flow cytometry (FCM), CCK-8, RNA-sequencing, Western blotting, RT-qPCR, immunofluorescence and ChIP assays were carried out in the HCC cells to investigate the effect of H2S on biological functions and JNK/JunB-TNFSF14 signaling pathway. Specimens from HCC patients were analyzed by RT-qPCR and Western blotting assays for evaluating the expression of TNFSF14 and CSE. Statistical analysis was used to analyze the correlation between TNFSF14 expression and clinical data of HCC patients. Based on the FCM and CCK-8 results, we found the LX-2 cells were able to induce HCC cells apoptosis through releasing H2S. RNA-sequencing, RT-qPCR, and Western blotting results showed that TNFSF14 gene was upregulated in both LX-2 and NaHS group. NaHS treated in HCC cells led to JNK/JunB signaling pathway activating and greater binding of p-JunB to its responsive elements on TNFSF14 promoter. Impairment of TNFSF14 induction alleviated LX-2 and NaHS induced apoptosis of HepG2 and PLC/PRF/5 cells. Furthermore, TNFSF14 expression in HCC tissues was lower than the adjacent tissue. HCC patients with low expression of TNFSF14 had higher malignant degree and poor prognosis. In summary, demonstration of the involvement of HSC-derived H2S in JNK/JunB mediated expression of TNFSF14 gene strongly indicates H2S palys an important role in the regulation of HCC apoptosis.Subject terms: Apoptosis, Liver cancer 相似文献
992.
993.
Lu Qiao Lili Men Shanshan Yu Junjie Yao Yu Li Mingming Wang Ying Yu Ning Wang Liyuan Ran Yingjie Wu Jianling Du 《Cell death & disease》2022,13(3)
Nonalcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), which are all complex metabolic disorders. Selenoprotein S (SelS) is an endoplasmic reticulum (ER) resident selenoprotein involved in regulating ER stress and has been found to participate in the occurrence and development of IR and T2DM. However, the potential role and mechanism of SelS in NAFLD remains unclear. Here, we analyzed SelS expression in the liver of high-fat diet (HFD)-fed mice and obese T2DM model (db/db) mice and generated hepatocyte-specific SelS knockout (SelSH-KO) mice using the Cre-loxP system. We showed that hepatic SelS expression levels were significantly downregulated in HFD-fed mice and db/db mice. Hepatic SelS deficiency markedly increased ER stress markers in the liver and caused hepatic steatosis via increased fatty acid uptake and reduced fatty acid oxidation. Impaired insulin signaling was detected in the liver of SelSH-KO mice with decreased phosphorylation levels of insulin receptor substrate 1 (IRS1) and protein kinase B (PKB/Akt), which ultimately led to disturbed glucose homeostasis. Meanwhile, our results showed hepatic protein kinase Cɛ (PKCɛ) activation participated in the negative regulation of insulin signaling in SelSH-KO mice. Moreover, the inhibitory effect of SelS on hepatic steatosis and IR was confirmed by SelS overexpression in primary hepatocytes in vitro. Thus, we conclude that hepatic SelS plays a key role in regulating hepatic lipid accumulation and insulin action, suggesting that SelS may be a potential intervention target for the prevention and treatment of NAFLD and T2DM.Subject terms: Metabolic syndrome, Obesity 相似文献
994.
Laboratory and field studies were conducted to evaluate freezing as a control measure against Brennandania lambi (Krczal) which infests cultivated mushrooms (Agaricus bisporus) in Shanghai primarily through contaminated spawn. Laboratory experiments showed that exposure of contaminated spawn at -10° C for 24 h killed all stages of B. lambi. These mites probably died due to the freezing of body tissues during sustained exposure at -10° C for 24 h. because the supercooling points for the egg, active larva, quiescent larva, non-gravid adult and gravid adult of B. lambi were respectively -11.34, -10.96, -11.43, -7.65 and -11.20° C, whereas the freezing points were respectively -6.68, -6.84. -6.56, -3.96 and -6.75 °C. Semi-field experiments showed that compost inoculated with B. lambi-infested spawn that had been exposed at -10 °C for 24 h had no mite infestation during spawn running and thus mycelium growth was normal. Laboratory and field experiments during 1989 to spring 1990 showed that freezing spawn had no effect on mushroom yield. Further field experiments in two farms during fall 1990 showed no effect of freezing spawn on yield in one farm and increased yield in the other farm. A field experiment during 1991 to 1992 also indicated that freezing spawn -10 °C for 24 h to 34 h had no effect on mushroom yield. 相似文献
995.
Molecular characterization and sequencing of antifreeze proteins from larvae of the beetle Dendroides canadensis 总被引:4,自引:0,他引:4
J. G. Duman N. Li D. Verleye F. W. Goetz D. W. Wu C. A. Andorfer T. Benjamin D. C. Parmelee 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1998,168(3):225-232
The deduced amino acid sequences of antifreeze proteins (AFPs) from larvae of the beetle Dendroides canadensis were determined from both complementary DNAs (cDNAs) and from peptide sequencing. These consisted of proteins with a 25-residue
signal peptide and mature proteins 83 (Dendroides antifreeze protein; DAFP-1) or 84 (DAFP-2) amino acids in length which differed at only two positions. Peptide sequencing
yielded sequences which overlapped exactly with those of the deduced cDNA sequences of DAFP-1 and DAFP-2, while the partial
sequence of another AFP (DAFP-3) matched 21 of 28 residues. Seven 12- or 13-mer repeating units are present in these antifreeze
proteins with a consensus sequence consisting of: Cys-Thr-X3-Ser-X5-X6-Cys-X8-X9-Ala-X11-Thr-X13, where X3 and X11 tend toward charged residues, X5 tends toward threonine or serine, X6 toward asparagine or aspartate, X9 toward asparagine or lysine, and X13 toward alanine in the 13-mers. The most interesting feature of these proteins is that throughout the length of the mature
antifreeze proteins every sixth residue is a cysteine. These sequences are not similar to any of the known fish AFPs, but
they are similar to AFPs from the beetle Tenebrio molitor.
Accepted: 14 November 1997 相似文献
996.
组织型纤溶酶原激活剂的纯化制备 总被引:1,自引:0,他引:1
简述了用于大规模生产组织型纤溶酶原激活剂(tPA)的重组动物细胞及其培养工艺。从重组tPA的大规模、快速纯化的角度考虑,对tPA的纯化制备方法进行了简要评述。 相似文献
997.
胸腺细胞在胸腺外凋亡的形态学证据 总被引:1,自引:0,他引:1
In vitro thymus explants culture designed in this paper can mimic the thymic microenvironment as it were in vivo. Theoretically, thymus explants are cut off free from blood stream. So if some developing or developed thymocytes had the inclination to migrate into the periphery, they would only be accumulated in the blood vessels within thymus explants. After 3-day's culture, under transmission electron microscope we observed the migrating thymocytes accumulated in the blood vessels of C57BL/6 mice thymus explants, and these thymocytes were occurring apoptosis at different stage. To our knowledge, this findings offers the first morphological evidence that thymocytes do not necessarily die inside the thymus in situ, and that having acquired the death signals thymocytes can migrate into the blood stream and die quickly outside the thymus. But this is not to say that we deny the intrathymic death hypothesis. On the contrary, we found the number of thymocytes occurring in situ apoptosis on the surfaces of stromal cells is far more than that of migrating into the blood vessels. So, our proposal is that there are two sites for thymocytes apoptosis, some die inside the thymus and the others die outside the thymus. 相似文献
998.
测定了棉铃虫(Helicoverpaarmigera)核型多角体病毒(HaSNPV)基因组DNA的HindIIK片段核苷酸序列。该片段全长3255bp,含可编码大于40个氨基酸残基的多肽的开放阅读框(ORF)15个,包括多角体蛋白(ph)基因编码区3′端489bp和蛋白激酶HavPK基因编码区801bp。在ph和HavPK两基因之间鉴定出一个可编码412个氨基酸残基的ORF1236,转录方向与ph和HavPK基因相反。同源分析表明,ORF1236与谷实夜蛾(Helicoverpazea)核型多角体病毒(HzSNPV)的ORF8推导的蛋白氨基酸序列有95.9%同源性,与苜蓿丫纹夜蛾(Autographacalifornia)核型多角体病毒(AcMNPV)ORF1629只有24.8%同源性,但三者均含有二组由多个脯氨酸残基串联而成的特征基序。 相似文献
999.
G Protein β Subunit–null Mutants Are Impaired in Phagocytosis and Chemotaxis Due to Inappropriate Regulation of the Actin Cytoskeleton 下载免费PDF全文
Barbara Peracino Jane Borleis Tian Jin Monika Westphal Jean-Marc Schwartz Lijun Wu Enrico Bracco Günther Gerisch Peter Devreotes Salvatore Bozzaro 《The Journal of cell biology》1998,141(7):1529-1537
Chemotaxis and phagocytosis are basically similar in cells of the immune system and in Dictyostelium amebae. Deletion of the unique G protein β subunit in D. discoideum impaired phagocytosis but had little effect on fluid-phase endocytosis, cytokinesis, or random motility. Constitutive expression of wild-type β subunit restored phagocytosis and normal development. Chemoattractants released by cells or bacteria trigger typical transient actin polymerization responses in wild-type cells. In β subunit–null cells, and in a series of β subunit point mutants, these responses were impaired to a degree that correlated with the defect in phagocytosis. Image analysis of green fluorescent protein–actin transfected cells showed that β subunit– null cells were defective in reshaping the actin network into a phagocytic cup, and eventually a phagosome, in response to particle attachment. Our results indicate that signaling through heterotrimeric G proteins is required for regulating the actin cytoskeleton during phagocytic uptake, as previously shown for chemotaxis. Inhibitors of phospholipase C and intracellular Ca2+ mobilization inhibited phagocytosis, suggesting the possible involvement of these effectors in the process. 相似文献
1000.
The seeds of Paris polyphylla var. yunnanensis are deeply dormant, and they remain dormant for 18 months or longer in their natural environment. Periodic exposure of the seeds to a low-temperature of 4 °C broke the dormancy in about 16 weeks (112 days). The most effective temperature stratification scheme was an interval of 14 days at 4 °C and 14 days at 22 °C. Both GA3 and ethephon significantly enhanced the germination rate during the stratification treatment. The seed coat, particularly the mesophyll outer layer of the seed coat, strongly inhibited the germination. With removal of the seed coat and exposure of the uncoated seeds to 600 mg/l GA3 for 48 h before the temperature stratification of 14 days at 4 °C and 14 days at 22 °C for 112 days, a germination percentage as high as 95.3% of the seeds was attained in about 160 days. 相似文献