全文获取类型
收费全文 | 8974篇 |
免费 | 527篇 |
国内免费 | 3篇 |
专业分类
9504篇 |
出版年
2022年 | 53篇 |
2021年 | 107篇 |
2020年 | 49篇 |
2019年 | 81篇 |
2018年 | 98篇 |
2017年 | 108篇 |
2016年 | 153篇 |
2015年 | 235篇 |
2014年 | 318篇 |
2013年 | 459篇 |
2012年 | 478篇 |
2011年 | 485篇 |
2010年 | 288篇 |
2009年 | 293篇 |
2008年 | 451篇 |
2007年 | 464篇 |
2006年 | 431篇 |
2005年 | 465篇 |
2004年 | 403篇 |
2003年 | 404篇 |
2002年 | 424篇 |
2001年 | 272篇 |
2000年 | 278篇 |
1999年 | 229篇 |
1998年 | 130篇 |
1997年 | 93篇 |
1996年 | 79篇 |
1995年 | 73篇 |
1994年 | 69篇 |
1993年 | 83篇 |
1992年 | 163篇 |
1991年 | 178篇 |
1990年 | 138篇 |
1989年 | 145篇 |
1988年 | 149篇 |
1987年 | 117篇 |
1986年 | 115篇 |
1985年 | 106篇 |
1984年 | 84篇 |
1983年 | 85篇 |
1982年 | 70篇 |
1981年 | 41篇 |
1980年 | 42篇 |
1979年 | 60篇 |
1978年 | 52篇 |
1976年 | 33篇 |
1975年 | 41篇 |
1974年 | 46篇 |
1973年 | 40篇 |
1971年 | 36篇 |
排序方式: 共有9504条查询结果,搜索用时 0 毫秒
991.
T Yoshimoto K Takahashi A Ajima A Matsushima Y Saito Y Tamaura Y Inada 《FEBS letters》1985,183(1):170-172
Modified asparaginase, in which 4 tryptophan residues were modified with 2-hydroxy-5-nitrobenzyl bromide, had little enzymic activity and retained immunoreactivity [(1976) FEBS Lett. 65, 11-15]. Addition of IgG or its Fab towards asparaginase to the modified asparaginase gave rise to marked enhancement of the enzymic activity. Native asparaginase (4 subunits) lost the enzymic activity due to dissociation into subunits by dilution of the enzyme solution. However, in the presence of Fab, asparaginase did not lose enzymic activity on dilution, probably due to no dissociation into subunits occurring. 相似文献
992.
A wasp venom mastoparan-induced polyphosphoinositide breakdown in rat peritoneal mast cells 总被引:7,自引:0,他引:7
The phospholipid metabolism of rat peritoneal mast cells stimulated with mastoparan, a secretagogue purified from wasp venom, was investigated. Mastoparan at 20 micrograms/ml caused a rapid secretion of histamine. Mastoparan induced a transient decrease of phosphatidylinositol 4,5-biphosphate on 32P labeling and generation of a water-soluble degradation product, inositol trisphosphate on [3H]inositol labeling, suggesting the activation of phospholipase C upon stimulation. 相似文献
993.
Atrial natriuretic factor increases cyclic GMP and inhibits cyclic AMP in rat renal papillary collecting tubule cells in culture 总被引:3,自引:0,他引:3
S Ishikawa T Saito K Okada T Kuzuya K Kangawa H Matsuo 《Biochemical and biophysical research communications》1985,130(3):1147-1153
The present study was undertaken to determine whether human atrial natriuretic factor (hANF) produces guanosine-3', 5'-monophosphate (cGMP) and alters arginine vasopressin (AVP)- and forskolin (F)- induced adenosine-3', 5'-monophosphate (cAMP) production in the cultured rat renal papillary collecting tubule cells. hANF increased cellular cGMP levels in a dose dependent manner. AVP and F, however, did not affect cGMP production. hANF significantly inhibited AVP- and F-stimulated cAMP levels, but hANF by itself did not affect cellular cAMP production. Since F activates adenylate cyclase at a step of catalytic unit and the cellular action of AVP to activate adenylate cyclase is mediated through receptor-catalytic units, the present results indicate that hANF may directly inhibit the AVP- and F-stimulated adenylate cyclase in renal papillary collecting tubules. 相似文献
994.
995.
We determined the complete nucleotide sequence of the mitochondrial genome (except for a portion of the putative control
region) for a deep-sea fish, Gonostoma gracile. The entire mitochondrial genome was purified by gene amplification using long polymerase chain reaction (long PCR), and the
products were subsequently used as templates for PCR with 30 sets of newly designed, fish-universal primers that amplify contiguous,
overlapping segments of the entire genome. Direct sequencing of the PCR products showed that the genome contained the same
37 mitochondrial structural genes as found in other vertebrates (two ribosomal RNA, 22 transfer RNA, and 13 protein-coding
genes), with the order of all rRNA and protein-coding genes, and 19 tRNA genes being identical to that in typical vertebrates.
The gene order of the three tRNAs (tRNAGlu, tRNAThr, and tRNAPro) relative to cytochrome b, however, differed from that determined in other vertebrates. Two steps of tandem duplication of gene regions, each followed
by deletions of genes, can be invoked as mechanisms generating such rearrangements of tRNAs. This is the first example of
tRNA gene rearrangements in a bony fish mitochondrial genome.
Received August 5, 1998; accepted February 19, 1999. 相似文献
996.
Allele-specific long-range PCR/sequencing method for allelic assignment of multiple single nucleotide polymorphisms 总被引:5,自引:0,他引:5
Nagano M Nakamura T Ozawa S Maekawa K Saito Y Sawada J 《Journal of biochemical and biophysical methods》2003,55(1):1-9
We report an allele-specific sequencing method using allele-specific long-range polymerase chain reaction (PCR) to determine if multiple (specifically, more than three) single nucleotide polymorphisms (SNPs) are located on the same allele. We sequenced the glucocorticoid receptor (GR) gene as a model and detected four nucleotide changes, including two novel variations, in intron 4 and exons 6, 8, and 9 alpha in four of the investigated cell lines. The terminal SNPs (intron 4 and exon 9 alpha) were separated by 19 kb. Following SNP identification, the first round PCR allele-specific primers are designed at the both distal SNP sites (intron 4 and exon 9 alpha), placing the SNP positions at the primer 3'-end. Using these first round PCR products as template, the second round PCR was performed to separately amplify exons 6 and 8. These second round PCR products were subsequently sequenced. The sequencing results showed that the four SNPs were located on the same allele, i.e., forming a haplotype. This allele-specific long-range PCR/sequencing (ALP/S) method is rapid and applicable to the allelic assignment for more than three SNPs. 相似文献
997.
Hirohito Mori Hideki Kobara Takaaki Tsushimi Noriko Nishiyama Shintaro Fujihara Tsutomu Masaki 《PloS one》2015,10(4)
Objective
Objective evaluation of resected specimen and tumor size is critical because the tumor diameter after endoscopic submucosal dissection affects therapeutic strategies. In this study, we investigated whether the true tumor diameter of gastrointestinal cancer specimens measured by flexible endoscopy is subjective by testing whether the specimen is correctly attached to the specimen board after endoscopic submucosal dissection resection and whether the size differs depending on the endoscopist who attached the specimen.Methods
Seventy-two patients diagnosed with early gastric cancer who satisfied the endoscopic submucosal dissection expanded-indication guideline were enrolled. Three endoscopists were randomly selected before every endoscopic submucosal dissection. Each endoscopist separately attached the same resected specimen, measured the maximum resection diameter and tumor size, and removed the lesion from the attachment board.Results
The resected specimen diameters of the 3 endoscopists were 44.5±13.9 mm (95% Confidence Interval (CI): 23–67), 37.4±12.0 mm (95% CI: 18–60), and 41.1±13.3 mm (95% CI: 20–63) mm. Comparison among 3 groups (Kruskal Wallis H- test), there were significant differences (H = 6.397, P = 0.040), and recorded tumor sizes were 38.3±13.1 mm (95% CI: 16–67), 31.1±11.2 mm (95% CI: 12.5–53.3), and 34.8±12.8 (95% CI: 11.5–62.3) mm. Comparison among 3 groups, there were significant differences (H = 6.917, P = 0.031).Conclusions
Human errors regarding the size of attached resected specimens are unavoidable, but it cannot be ignored because it affects the patient’s additional treatment and/or surgical intervention. We must develop a more precise methodology to obtain accurate tumor size.Trial Registration
University hospital Medical Information Network UMIN No. 000012915 相似文献998.
Tumor necrosis factor as an activator of human granulocytes. Potentiation of the metabolisms triggered by the Ca2+-mobilizing agonists 总被引:3,自引:0,他引:3
A Yuo S Kitagawa I Suzuki A Urabe T Okabe M Saito F Takaku 《Journal of immunology (Baltimore, Md. : 1950)》1989,142(5):1678-1684
TNF stimulated superoxide (O2-) release directly in human granulocytes in a dose-dependent manner (1 to 1000 U/ml), although its potency was weak. TNF-induced O2- release was inhibited by cAMP agonists or ionomycin, and was not accompanied with an increase in cytoplasmic free Ca2+ [( Ca2+]i) and membrane potential changes (depolarization). These findings indicate that neither Ca2+ mobilization nor membrane depolarization is required for TNF-receptor-mediated cell activation. The pretreatment of human granulocytes with TNF enhanced O2- release and membrane depolarization in parallel stimulated by the receptor-mediated Ca2+-mobilizing agonists (FMLP, Con A, and wheat germ agglutinin) or the Ca2+ ionophore ionomycin, but not by PMA, a direct activator of protein kinase C. The optimal effect was obtained by pretreatment of cells with 100 U/ml TNF for 5 to 10 min at 37 degrees C, although the magnitude of enhancement varied according to the agonists used as subsequent stimuli. TNF did not affect an increase in [Ca2+]i stimulated by the Ca2+-mobilizing agonists, except Con A. Con A-induced increase in [Ca2+]i was enhanced by TNF in a dose-dependent manner. These diverse effects of TNF could be partly explained by the exclusive potentiation by TNF of the metabolic events triggered by an increase in [Ca2+]i. 相似文献
999.
Molecular distinction between pathogenic and infectious properties of the prion protein 总被引:6,自引:0,他引:6 下载免费PDF全文
Chiesa R Piccardo P Quaglio E Drisaldi B Si-Hoe SL Takao M Ghetti B Harris DA 《Journal of virology》2003,77(13):7611-7622
Tg(PG14) mice express a prion protein (PrP) with a nine-octapeptide insertion associated with a human familial prion disease. These animals spontaneously develop a fatal neurodegenerative disorder characterized by ataxia, neuronal apoptosis, and accumulation in the brain of an aggregated and weakly protease-resistant form of mutant PrP (designated PG14(spon)). Brain homogenates from Tg(PG14) mice fail to transmit disease after intracerebral inoculation into recipient mice, indicating that PG14(spon), although pathogenic, is distinct from PrP(Sc), the infectious form of PrP. In contrast, inoculation of Tg(PG14) mice with exogenous prions of the RML strain induces accumulation of PG14(RML), a PrP(Sc) form of the mutant protein that is infectious and highly protease resistant. Like PrP(Sc), both PG14(spon) and PG14(RML) display conformationally masked epitopes in the central and octapeptide repeat regions. However, these two forms differ profoundly in their oligomeric states, with PG14(RML) aggregates being much larger and more resistant to dissociation. Our analysis provides new molecular insight into an emerging puzzle in prion biology, the discrepancy between the infectious and neurotoxic properties of PrP. 相似文献
1000.
Yuki Nakayama Akiko Yamamoto Masaki Tanaka Atsunori Fukuhara Iichiro Shimomura 《Biochemical and biophysical research communications》2009,379(2):288-292
Rho GTPase regulates actin cytoskeleton organization and assembly in many cell types, however, its significance in adipose tissue is not well characterized. Here, we demonstrate high RhoA activity in adipose tissues of C57BL/6J mice. To determine the effect of RhoA activation on 3T3-L1 cells, stable cell lines overexpressing G14VRhoA fused to destabilizing domain of FKBP12 (DD-G14VRhoA-L1) were generated. Treatment of DD-G14VRhoA-L1 cells with Shield1 following their differentiation into adipocytes, resulted in the appearance of thick cortical actin filaments, and increased the mRNA expression levels of plasminogen activator inhibitor type-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1). The induction of PAI-1 and MCP-1 was inhibited by treatment with a Rho-associated kinase (ROCK) inhibitor, Y-27632. In 3T3-L1 adipocytes, tumor necrosis factor-α activated RhoA and increased mRNA expression of PAI-1 and MCP-1, and their treatment with Y-27632 partially inhibited these changes. The results indicate that RhoA-ROCK pathway induces inflammatory cytokine expression in adipocytes. 相似文献