全文获取类型
收费全文 | 932篇 |
免费 | 60篇 |
专业分类
992篇 |
出版年
2023年 | 2篇 |
2022年 | 7篇 |
2021年 | 7篇 |
2020年 | 6篇 |
2019年 | 13篇 |
2018年 | 20篇 |
2017年 | 19篇 |
2016年 | 27篇 |
2015年 | 41篇 |
2014年 | 35篇 |
2013年 | 64篇 |
2012年 | 70篇 |
2011年 | 86篇 |
2010年 | 57篇 |
2009年 | 48篇 |
2008年 | 62篇 |
2007年 | 54篇 |
2006年 | 64篇 |
2005年 | 60篇 |
2004年 | 56篇 |
2003年 | 49篇 |
2002年 | 33篇 |
2001年 | 10篇 |
1999年 | 6篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 8篇 |
1990年 | 2篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1974年 | 5篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1966年 | 1篇 |
1962年 | 2篇 |
排序方式: 共有992条查询结果,搜索用时 0 毫秒
31.
32.
33.
Shevelev I Blanca G Villani G Ramadan K Spadari S Hübscher U Maga G 《Nucleic acids research》2003,31(23):6916-6925
DNA polymerase (pol) λ is homologous to pol β and has intrinsic polymerase and terminal transferase activities. However, nothing is known about the amino acid residues involved in these activites. In order to precisely define the nucleotide-binding site of human pol λ, we have mutagenised two amino acids, Tyr505 and the neighbouring Phe506, which were predicted by structural homology modelling to correspond to the Tyr271 and Phe272 residues of pol β, which are involved in nucleotide binding. Our analysis demonstrated that pol λ Phe506Arg/Gly mutants possess very low polymerase and terminal transferase activities as well as greatly reduced abilities for processive DNA synthesis and for carrying on translesion synthesis past an abasic site. The Tyr505Ala mutant, on the other hand, showed an altered nucleotide binding selectivity to perform the terminal transferase activity. Our results suggest the existence of a common nucleotide-binding site for the polymerase and terminal transferase activities of pol λ, as well as distinct roles of the amino acids Tyr505 and Phe506 in these two catalytic functions. 相似文献
34.
35.
Giacometti A Cirioni O Antonicelli L D'Amato G Silvestri C Del Prete MS Scalise G 《The Journal of parasitology》2003,89(3):490-492
The prevalence of intestinal protozoans and helminths in stool samples of individuals with allergic cutaneous symptoms was evaluated to study a possible link between parasites and allergy. Altogether, 218 patients who had chronic urticaria, atopic dermatitis, or pruritus of unknown origin were included in the study. Standard laboratory tests for the detection of allergic etiology were performed for all patients. The presence of intestinal parasites was investigated using microscopy, immunofluorescence, and immunoenzymatic assays. Overall, protozoans and helminths were recovered from the stools of 48 subjects (P = 0.004), 18 of whom were affected with intestinal symptoms (P = 0.023). The presence of Giardia lamblia in the stools was significantly associated with allergic cutaneous manifestations (P = 0.030). In addition, patients with allergy were significantly more likely to have > or = 5 Blastocystis hominis organisms per field (P = 0.046). There was a set of patients with allergic cutaneous diseases in whom the presence of intestinal parasites may not be incidental. 相似文献
36.
There is growing evidence that high concentrations of nitric oxide (NO), generated by activated astrocytes, might be involved in a variety of neurodegenerative diseases, such as Alzheimer's disease, ischemia and epilepsy. It has recently been suggested that glial cells may produce NO under superoxide radical stimulation by enzyme-independent mechanism. This suggests that also natural antioxidants may have therapeutical relevance in neurodegenerative diseases. Studies of Bhattacharya et al. have evidenced that Bacopa monniera (BM) (family Scrophulariaceae), an Ayurvedic medicinal plant clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative, is able to reduce the memory-dysfunction in rat models of Alzheimer's disease, but the molecular mechanisms of this action are yet to be determined. In the present study, we examined the effect of a methanolic extract of BM on toxicity induced by the nitric oxide donor, S-nitroso-N-acetyl-penicillamine (SNAP), in culture of purified rat astrocytes. Our results indicate that, after 18 h of treatment, SNAP induced an increase in the production of reactive species, but did not induce the rupture of cellular membrane. Conversely, this NO donor induced a fragmentation of genomic DNA compared to control astrocytes. The extract of BM inhibited the formation of reactive species and DNA damage in a dose dependent manner. This data supports the traditional use of BM and indicates that this medicinal plant has a therapeutic potential in treatment or prevention of neurological diseases. 相似文献
37.
38.
Copper amine oxidase expression in defense responses to wounding and Ascochyta rabiei invasion 总被引:2,自引:0,他引:2 下载免费PDF全文
Wounding chickpea (Cicer arietinum) internodes or cotyledons resulted in an increase in the steady-state level of copper amine oxidase (CuAO) expression both locally and systemically. Dissection of the molecular mechanisms controlling CuAO expression indicated that jasmonic acid worked as a potent inducer of the basal and wound-inducible CuAO expression, whereas salicylic acid and abscisic acid caused a strong reduction of the wound-induced CuAO expression, without having any effect on the basal levels. Epicotyl treatment with the CuAO mechanism-based inhibitor 2-bromoethylamine decreased hydrogen peroxide (H(2)O(2)) levels in all the internodes, as evidenced in vivo by 3,3'-diaminobenzidine oxidation. Moreover, inhibitor pretreatment of wounded epicotyls resulted in a lower accumulation of H(2)O(2) both at the wound site and in distal organs. In vivo CuAO inhibition by 2-bromoethylamine after inoculation of resistant chickpea cv Sultano with Ascochyta rabiei resulted in the development of extended necrotic lesions, with extensive cell damage occurring in sclerenchyma and cortical parenchyma tissues. These results, besides stressing the fine-tuning by key signaling molecules in wound-induced CuAO regulation, demonstrate that local and systemic CuAO induction is essential for H(2)O(2) production in response to wounding and indicate the relevance of these enzymes in protection against pathogens. 相似文献
39.
40.
De Stefanis D Reffo P Bonelli G Baccino FM Sala G Ghidoni R Codogno P Isidoro C 《Biological chemistry》2002,383(6):989-999
Ceramide has been suggested as an important mediator of apoptosis. In HT-29 colorectal cancer cells increased ceramide levels, induced by exogenous N-acetylsphingosine (NAS, also known as C2-ceramide) or by 1-phenyl-2-(decanoylamino)-3-morpholino-1-propanol (PDMP), inhibited the transport and processing of cathepsin D (CD), a lysosomal protease implicated in apoptosis of tumour cells. C2-dihydroceramide (DH-C2), an inactive analogue of NAS, had no effect on CD transport and maturation. The treatment with either NAS or PDMP was revealed to be cytotoxic for HT-29 cells and led to cell death with classical features of apoptosis. Morphological signs of apoptosis and DNA fragmentation became apparent only between 24 and 48 h of incubation and poly(ADP ribose)-polymerase cleavage, a hallmark of caspase 3 activity, occurred no earlier than 8 h from incubation. Secretion of proCD was almost abolished and the formation of double-chain mature CD was reduced and delayed by NAS, whereas PDMP largely inhibited the lysosomal targeting and maturation of proCD. NAS- and PDMP-induced alteration of proCD transport and maturation were apparent already 2 h after incubation with the drugs, which is much earlier than when classical biochemical and morphological evidence of apoptosis could be detected. These data indicate that alteration of CD (and possibly of other glycoproteins) transport along the secretory pathway due to increased levels of cell-associated ceramide is an early event in cells undergoing apoptosis. 相似文献