全文获取类型
收费全文 | 1352篇 |
免费 | 47篇 |
国内免费 | 7篇 |
出版年
2024年 | 2篇 |
2023年 | 14篇 |
2022年 | 58篇 |
2021年 | 97篇 |
2020年 | 27篇 |
2019年 | 46篇 |
2018年 | 40篇 |
2017年 | 33篇 |
2016年 | 57篇 |
2015年 | 60篇 |
2014年 | 79篇 |
2013年 | 108篇 |
2012年 | 119篇 |
2011年 | 99篇 |
2010年 | 43篇 |
2009年 | 58篇 |
2008年 | 62篇 |
2007年 | 65篇 |
2006年 | 55篇 |
2005年 | 64篇 |
2004年 | 38篇 |
2003年 | 39篇 |
2002年 | 24篇 |
2001年 | 10篇 |
2000年 | 9篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 12篇 |
1994年 | 7篇 |
1993年 | 8篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1973年 | 1篇 |
1970年 | 2篇 |
排序方式: 共有1406条查询结果,搜索用时 15 毫秒
51.
Khalid O. Alfarouk 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):859-866
Cancer cells reprogram their metabolic machineries to enter into permanent glycolytic pathways. The full reason for such reprogramming takes place is unclear. However, this metabolic switch is not made in vain for the lactate that is generated and exported outside cells is reused by other cells. This results in the generation of a pH gradient between the low extracellular pH that is acidic (pHe) and the higher cytosolic alkaline or near neutral pH (pHi) environments that are tightly regulated by the overexpression of several pumps and ion channels (e.g. NHE-1, MCT-1, V-ATPase, CA9, and CA12). The generation of this unique pH gradient serves as a determining factor in defining “tumor fitness”. Tumor fitness is the capacity of the tumor to invade and metastasize due to its ability to reduce the efficiency of the immune system and confer resistance to chemotherapy. In this article, we highlight the importance of tumor microenvironment in mediating the failure of chemotherapeutic agents. 相似文献
52.
53.
Khalid A. Al-Hothaly Mohamed Taha Brian H. May Stella Stylianou Andrew S. Ball Eric M. Adetutu 《欧洲藻类学杂志》2016,51(1):1-10
The green alga Botryococcus braunii is widely recognized as a source of non-fossil oil. However, limitations in Botryococcus biomass production hamper its commercial exploitation. This study examines the effects of nutrients (nitrogen and iron) and environmental conditions (temperature, light intensity and photoperiod) on biomass and oil production in two B. braunii Race B strains, Kossou-4 and Overjuyo-3. The highest biomass and oil production were obtained at a nitrogen concentration of 750 mg l?1, iron concentration of 6 mg l?1, at 25°C and at 135 µmol photons m?2 s?1 with a photoperiod of 16 h light:8 h darkness. Culturing the strains in Blue-green (BG11) medium containing optimized nutrients under optimal conditions resulted in an up to ~10.6-fold increase in biomass. In Kossou-4 and Overjuyo-3 strains, biomass increased from 1.647 g 10 l?1 and 3.137 g 10 l?1 respectively in normal BG11 medium to 17.390 g 10 l?1 and 21.721 g 10 l?1 in optimized BG11 media and growth conditions. This was accompanied by ~8–10.5-fold increase in oil production compared with that in normal BG11 medium. Oil (0.324 g 10 l?1 and 0.211 g 10 l?1) was produced in normal BG11 medium in Kossou-4 and Overjuyo-3 strains respectively, compared with 2.642 g 10 l?1 (Kossou-4) and 2.206 g 10 l?1 (Overjuyo-3) in modified BG11 media under optimized conditions. Therefore, optimization of nutrients and environmental conditions can increase biomass and oil production in the two strains of B. braunii. 相似文献
54.
Iqbal Tahir Ijaz Mohsin Javaid Muhammad Rafique Muhammad Riaz Khalid Nadeem Tahir Muhammad Bilal Nabi Ghulam Abrar Muhammad Afsheen Sumera 《Plasmonics (Norwell, Mass.)》2019,14(1):147-154
Plasmonics - Effect of different gold (Au) grating structures on light absorption in solar cell is investigated by finite elemental analysis using COMSOL multiphysics-RF module. The geometry of the... 相似文献
55.
Haseeb A. Khan Salman Alamery Khalid E. Ibrahim Doaa M. El-Nagar Najla Al-Harbi Mohamad Rusop Salman H. Alrokayan 《Saudi Journal of Biological Sciences》2019,26(3):625-631
Gold nanoparticles (GNPs) are among the ideal nano-sized materials for medical applications such as imaging and drug delivery. Considering the significance of recent reports on acute phase induction of inflammatory mediators by GNPs, we studied the effect of GNPs on proinflammatory cytokines gene expression in mouse brain. Group 1 served as control whereas groups 2–4 were given only one intraperitoneal dose of 5, 20 and 50?nm GNPs, respectively and sacrificed after 24?h. The animals in groups 5–7 also received the same treatment but sacrificed after 7?days. Groups 8–10 received two injections of GNPs (5, 20 and 50?nm, respectively), first at the beginning of study and second on day 6, and sacrificed on day 7. Total RNA was extracted from the cerebral tissue and analyzed for the gene expressions of IL-1β, IL-6 and TNF-α. A single injection of 5?nm diameter GNPs significantly increased the mRNA expression of IL-1β and IL-6 in mouse brain on day 7, which was not augmented by the second dose of the same GNPs. Larger size GNPs (20?nm and 50?nm) did not cause any significant change in the expression of proinflammatory cytokines in mouse brain. In conclusion, systemic administration of small sized GNPs (5?nm) induced a proinflammatory cascade in mouse brain indicating a crucial role of GNPs size on immune response. It is important to use the right sized GNPs in order to avoid an acute phase inflammatory response that could be cytotoxic or interfere with the bioavailability of nanomaterials. 相似文献
56.
Nuru Adgaba Ahmad Al-Ghamdi Yilma Tadesse Ramzi Alsarhan Arif Single Seif Eldin Mohammed Khalid Ali Khan 《Saudi Journal of Biological Sciences》2019,26(7):1649-1654
In the current study, we investigated if any variations exist in acceptance rate of grafted larvae and quality of queens reared in different queen cell cup sizes, between wet and dry grafting and between queen right and queen less conditions of A. m. jemenitica colonies. The acceptance rate of grafted larvae in different queen cell cup sizes (7.0 mm, 7.5 mm, 8.0 mm, 8.5 mm) were varying from 69 to 71% and the variations were not significant among the different queen cups sizes but averagely lower than the acceptances recorded for other races. Out of the 172 dry grafted larvae, only 56.4% of them were accepted while in wet grafting out of 174 grafted larvae 77.01% were accepted. Regarding the rate of sealing, 48.84% and 71.84% of them sealed for dry and wet grafts, respectively. The observed variation in the rate of acceptance and sealing were significant (N = 346, df = 1, P < 0.0001) between the two techniques. However, there was no significant difference in fresh weight of emerged queens between the two grafting methods. Out of the 324 grafted larvae given to queen right and queen less starter colonies each; 106 (32.72%) and 252 (73.68%) were accepted in queen right and queen less starter colonies, respectively and the variation was highly significant at P < 0.0001. The total number of sealed pupae were 82 (25.31%) and 216 (63.16%) for queen right and queen less colonies, respectively and the variations was significant at P < 0.0001. From the study it can be concluded that A. m. jemenitica colonies can rear significantly more queens under wet grafting and in queen less colonies conditions than dry grafting and queen right conditions 相似文献
57.
Muhammad Taha Sadia Sultan Syahrul Imran Fazal Rahim Khalid Zaman Abdul Wadood Ashfaq Ur Rehman Nizam Uddin Khalid Mohammed Khan 《Bioorganic & medicinal chemistry》2019,27(18):4081-4088
In searchof the potenttherapeutic agent as an α-glucosidase inhibitor, we have synthesized twenty-five analogs (1–25) of quinoline-based Schiff bases as an inhibitoragainst α-glucosidase enzyme under positive control acarbose (IC50 = 38.45 ± 0.80 µM). From the activity profile it was foundthat analogs 1, 2, 3, 4, 11, 12 and 20with IC50values 12.40 ± 0.40, 9.40 ± 0.30, 14.10 ± 0.40, 6.20 ± 0.30, 14.40 ± 0.40, 7.40 ± 0.20 and 13.20 ± 0.40 µMrespectively showed most potent inhibition among the series even than standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Here in the present study analog 4 (IC50 = 6.20 ± 0.30 µM) was found with many folds better α-glucosidase inhibitory activity than the reference drug. Eight analogs like 5, 7, 8, 16, 17, 22, 24 and 25 among the whole series displayed less than 50% inhibition. The substituents effects on phenyl ring thereby superficially established through SAR study. Binding interactions of analogs and the active site of ligands proteins were confirmed through molecular docking study. Spectroscopic techniques like 1H NMR, 13C NMR and ESIMS were used for characterization. 相似文献
58.
Oberprieler NG Roberts W Riba R Graham AM Homer-Vanniasinkam S Naseem KM 《FEBS letters》2007,581(7):1529-1534
We examined the influence of S-nitrosoglutathione (GSNO) on alpha(IIb)beta(3) integrin-mediated platelet adhesion to immobilised fibrinogen. GSNO induced a time- and concentration-dependent inhibition of platelet adhesion. Inhibition was cGMP-independent and associated with both reduced platelet spreading and protein tyrosine phosphorylation. To investigate the cGMP-independent effects of NO we evaluated integrin beta(3) phosphorylation. Adhesion to fibrinogen induced rapid phosphorylation of beta(3) on tyrosines 773 and 785, which was reduced by GSNO in a cGMP independent manner. Similar results were observed in suspended platelets indicating that NO-induced effects were independent of spreading-induced signalling. This is the first demonstration that NO directly regulates integrin beta(3) phosphorylation. 相似文献
59.
60.
The activity of the Wiskott-Aldrich syndrome-related WAVE3 protein is critical for the regulation of the Arp2/3-dependent cytoskeleton organization downstream of Rac-GTPase. The Ableson (Abl) non-receptor tyrosine kinase is also involved in the remolding of actin cytoskeleton in response to extracellular stimuli. Here we show that platelet-derived growth factor stimulation of cultured cells results in WAVE3-Abl interaction and localization to the cell periphery. WAVE3-Abl interaction promotes the tyrosine phosphorylation of WAVE3 by Abl, and STI-571, a specific inhibitor of Abl kinase activity, abrogates the Abl-mediated phosphorylation of WAVE3. We have also shown that Abl targets and phosphorylates four tyrosine residues in WAVE3 and that the Abl-dependent phosphorylation of WAVE3 is critical for the stimulation of lamellipodia formation and cell migration. Our results show that the activation of WAVE3 to promote actin remodeling is enhanced by the c-Abl-mediated tyrosine phosphorylation of WAVE3. 相似文献