全文获取类型
收费全文 | 804篇 |
免费 | 46篇 |
国内免费 | 8篇 |
专业分类
858篇 |
出版年
2022年 | 6篇 |
2021年 | 13篇 |
2018年 | 3篇 |
2017年 | 6篇 |
2016年 | 16篇 |
2015年 | 38篇 |
2014年 | 32篇 |
2013年 | 40篇 |
2012年 | 62篇 |
2011年 | 52篇 |
2010年 | 36篇 |
2009年 | 29篇 |
2008年 | 35篇 |
2007年 | 31篇 |
2006年 | 42篇 |
2005年 | 24篇 |
2004年 | 19篇 |
2003年 | 16篇 |
2002年 | 20篇 |
2001年 | 25篇 |
2000年 | 25篇 |
1999年 | 17篇 |
1998年 | 4篇 |
1997年 | 8篇 |
1996年 | 12篇 |
1995年 | 11篇 |
1993年 | 9篇 |
1992年 | 20篇 |
1991年 | 12篇 |
1990年 | 10篇 |
1989年 | 9篇 |
1988年 | 11篇 |
1987年 | 11篇 |
1986年 | 5篇 |
1985年 | 14篇 |
1984年 | 14篇 |
1983年 | 11篇 |
1982年 | 13篇 |
1981年 | 13篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 12篇 |
1977年 | 7篇 |
1976年 | 9篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1972年 | 3篇 |
1969年 | 3篇 |
1963年 | 3篇 |
1950年 | 3篇 |
排序方式: 共有858条查询结果,搜索用时 15 毫秒
1.
2.
Yu-Jen Chang U-Ser Jeng Ya-Ling Chiang Ing-Shouh Hwang Yun-Ru Chen 《The Journal of biological chemistry》2016,291(10):4903-4911
Hexanucleotide expansions, GGGGCC, in the non-coding regions of the C9orf72 gene were found in major frontotemporal lobar dementia and amyotrophic lateral sclerosis patients (C9FTD/ALS). In addition to possible RNA toxicity, several dipeptide repeats (DPRs) are translated through repeat-associated non-ATG-initiated translation. The DPRs, including poly(GA), poly(GR), poly(GP), poly(PR), and poly(PA), were found in the brains and spinal cords of C9FTD/ALS patients. Among the DPRs, poly(GA) is highly susceptible to form cytoplasmic inclusions, which is a characteristic of C9FTD/ALS. To elucidate DPR aggregation, we used synthetic (GA)15 DPR as a model system to examine the aggregation and structural properties in vitro. We found that (GA)15 with 15 repeats fibrillates rapidly and ultimately forms flat, ribbon-type fibrils evidenced by transmission electron microscopy and atomic force microscopy. The fibrils are capable of amyloid dye binding and contain a characteristic cross-β sheet structure, as revealed by x-ray scattering. Furthermore, using neuroblastoma cells, we demonstrated the neurotoxicity and cell-to-cell transmission property of (GA)15 DPR. Overall, our results show the structural and toxicity properties of GA DPR to facilitate future DPR-related therapeutic development. 相似文献
3.
4.
植物体内的钙信使系绕 总被引:6,自引:0,他引:6
Ca对植物不仅仅是一种大量营养元素,更重要的是作为偶连胞外信号与胞内生理生化反应的第二信使,作为植物代谢和发育的主要调控者。本文介绍了Ca在植物细胞中的分布及其体内平衡机制,以及Ca2+信使系统调控的植物生理生化过程,讨论了外界信号通过Ca2+信使系统的传递和表达过程,Ca2+信使系统对基因表达的可能影响,以及Ca2+信使系统的作用机制,并提出了今后的研究方向。 相似文献
5.
6.
Recombinant adenovirus encoding H-ras ribozyme induces apoptosis in laryngeal cancer cells through caspase- and mitochondria-dependent pathways 总被引:2,自引:0,他引:2
Wang CH Tsai LJ Tsao YP Hsieh JT Chien WW Liao CL Wang HW Liu HS Chen SL 《Biochemical and biophysical research communications》2002,298(5):805-814
Previously, we designed a ribozyme that targets the H-ras oncogene at the 12th codon mutation site (Chang et al., 1997). Ribozymes have antisense molecule and site-specific ribonuclease potential. In this study, an adenoviral vector was used to transduce the H-ras ribozyme into laryngeal cancer cells (HEp-2). This served to downregulate the H-ras gene expression in which this ribozyme performed antisense activity due to HEp-2 cells containing wild-type alleles in the 12th H-ras codon. Together, our data demonstrated that the recombinant adenovirus encoding H-ras ribozyme can be broadly regarded as a cytotoxic gene therapy in laryngeal cancer cells regardless of containing wild-type or mutant ras gene. In addition, the mechanism through which the H-ras ribozyme inhibited tumor growth was apoptosis and involved both caspase- and mitochondria-mediated pathways. The activators caspase-8 and -9 as well as the effector caspase-3 in the induction phase of apoptosis and the substrate PARP of caspase-3 in the execution phase were activated 48h following the H-ras ribozyme treatment. Mitochondrial events characterized by the production of superoxide anion and the release of cytochrome c started at 24h. Mitochondrial transmembrane potential loss occurred 48h after the ribozyme treatment. However, Bcl-2 delayed cytochrome c release to the cytosol, but it could not protect the apoptosis effect, suggesting that cytochrome c release from mitochondria may not play a role in H-ras ribozyme-induced apoptosis. 相似文献
7.
Preparation of cellodextrins using sulfuric acid 总被引:1,自引:0,他引:1
8.
Chih-Hua Tseng Chang-Sheng Lin Pin-Keng Shih Lo-Ti Tsao Jih-Pyang Wang Chih-Mei Cheng Cherng-Chyi Tzeng Yeh-Long Chen 《Bioorganic & medicinal chemistry》2009,17(18):6773-6779
Synthesis and anti-inflammatory effects of certain furo[3′,2′:3,4]naphtho[1,2-d]imidazole derivatives 12–18 were studied. These compounds were synthesized from naphtho[1,2-b]furan-4,5-dione (10) which in turn was prepared from the known 2-hydoxy-1,4-naphthoquinone (7) in a one pot reaction. Furo[3′,2′:3,4]naphtho[1,2-d]imidazole (12) was inactive (IC50 value of >30 μM) while its 5-phenyl derivative 13, with an IC50 value of 16.3 and 11.4 μM against lysozyme and β-glucuronidase release, respectively, was comparable to the positive trifluoperazine. The same potency was observed for 5-furan derivative 16 with an IC50 value of 19.5 and 11.3 μM against lysozyme and β-glucuronidase release, respectively. An electron-withdrawing NO2 substituted on 5-phenyl or 5-furanyl group led to the devoid of activity as in the cases of 14 and 17. Among them, compound 15 exhibited significant inhibitory effects, with an IC50 value of 7.4 and 5.0 μM against lysozyme and β-glucuronidase release, respectively.For the LPS-induced NO production, the phenyl derivatives 12–15 were inactive while the nitrofuran counterparts 17 and 18 suppress LPS-induced NO production significantly, with an IC50 value of 1.5 and 1.3 μM, respectively, which are more active than that of the positive 1400 W. Compounds 16–18 were capable of inhibiting LPS-induced iNOS protein expression at a dose-dependent manner in which compound 18, with an IC50 of 0.52 μM in the inhibition of iNOS expression, is approximately fivefold more potent than that of the positive 1400 W. In the CLP rat animal model, compound 18 was found to be more active than the positive hydrocortisone in the inhibition of the iNOS mRNA expression in rat lung tissue. The sepsis-induced PGE2 production in rat serum decreased 150% by the pretreatment of 18 in a dose of 10 mg/kg. 相似文献
9.
Cheng-Ming Tsao Jhih-Gang Jhang Shiu-Jen Chen Shuk-Man Ka Tao-Cheng Wu Wen-Jinn Liaw Hsieh-Chou Huang Chin-Chen Wu 《PloS one》2014,9(9)
Selegiline, an anti-Parkinson drug, has antioxidant and anti-apoptotic effects. To explore the effect of selegiline on sepsis, we used a clinically relevant animal model of polymicrobial sepsis. Cecal ligation and puncture (CLP) or sham operation was performed in male rats under anesthesia. Three hours after surgery, animals were randomized to receive intravenously selegiline (3 mg/kg) or an equivalent volume of saline. The administration of CLP rats with selegiline (i) increased arterial blood pressure and vascular responsiveness to norepinephrine, (ii) reduced plasma liver and kidney dysfunction, (iii) attenuated metabolic acidosis, (iv) decreased neutrophil infiltration in liver and lung, and (v) improved survival rate (from 44% to 65%), compared to those in the CLP alone rats. The CLP-induced increases of plasma interleukin-6, organ superoxide levels, and liver inducible nitric oxide synthase and caspase-3 expressions were ameliorated by selegiline treatment. In addition, the histological changes in liver and lung were significantly attenuated in the selegiline -treated CLP group compared to those in the CLP group. The improvement of organ dysfunction and survival through reducing inflammation, oxidative stress and apoptosis in peritonitis-induced sepsis by selegiline has potential as an adjuvant agent for critical ill. 相似文献
10.
Techniques for preparing hydrogel membrane capsules 总被引:1,自引:0,他引:1
Summary Techniques for preparing four kinds of hydrogel membrane capsules are described. In the present process the material being encapsulated remains in its original environment in an aqueous suspension. Also, capsule characteristics such as size, membrane thickness, pore-size and surface charge can be controlled over a wide range. 相似文献