全文获取类型
收费全文 | 958篇 |
免费 | 61篇 |
专业分类
1019篇 |
出版年
2024年 | 2篇 |
2023年 | 2篇 |
2022年 | 9篇 |
2021年 | 7篇 |
2020年 | 6篇 |
2019年 | 13篇 |
2018年 | 20篇 |
2017年 | 19篇 |
2016年 | 28篇 |
2015年 | 42篇 |
2014年 | 36篇 |
2013年 | 65篇 |
2012年 | 73篇 |
2011年 | 88篇 |
2010年 | 58篇 |
2009年 | 48篇 |
2008年 | 64篇 |
2007年 | 54篇 |
2006年 | 65篇 |
2005年 | 60篇 |
2004年 | 58篇 |
2003年 | 50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 | 5篇 |
1993年 | 7篇 |
1992年 | 3篇 |
1991年 | 8篇 |
1990年 | 2篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 2篇 |
1985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 |
1970年 | 2篇 |
1969年 | 2篇 |
1966年 | 1篇 |
1962年 | 2篇 |
排序方式: 共有1019条查询结果,搜索用时 0 毫秒
961.
Paesano N Marzocco S Vicidomini C Saturnino C Autore G De Martino G Sbardella G 《Bioorganic & medicinal chemistry letters》2005,15(3):539-543
Novel benzyl- and phenyl-isothioureidic derivatives have been synthesised and evaluated as inhibitors of nitric oxide synthesis, induced in lipopolysaccharide (LPS)-activated J774.A1 macrophage cell line. The most potent iNOS inhibitor resulting was 1-methyl-3-phenyl-S-methyl isothiourea 5l. 相似文献
962.
Haack T Fattori R Napoletano M Pellacini F Fronza G Raffaini G Ganazzoli F 《Bioorganic & medicinal chemistry》2005,13(14):4425-4433
This report describes the detailed conformational analysis and synthesis of a series of phthalazine phosphodiesterase-type (IV) (PDE IV) inhibitors bearing either mono- or dichloro 4-methylenepyridine at the 'down' position of the phthalazine nucleus or different heterocycles at the 'top' position 4 of the phthalazine moiety. Both the mono- and dichloro 4-methylenepyridine units linked at carbon C1 of the phthalazine nucleus show identical conformational behaviour with the substituent preferentially oriented towards the external part of the molecule and the pyridine plane almost orthogonal to that of phthalazine ring. The heterocyclic five-membered rings linked at carbon C4 of phthalazine show quite different conformational behaviour. The 1,3-thiazole ring exists in a well-defined conformation almost coplanar with respect to the phthalazine nucleus while the 1,2,4-triazole and the 1,3-diazole heterocycles show a great conformational freedom with large torsion angles. Compound 3 bearing the thiazole ring at C4 displays the major biological activity, thus suggesting that a planar and rather rigid conformation of the pentacycle should favour the PDE IV inhibition capacity of this class of compounds. 相似文献
963.
An integrated structural and computational study of the thermostability of two thioredoxin mutants from Alicyclobacillus acidocaldarius 下载免费PDF全文
Bartolucci S De Simone G Galdiero S Improta R Menchise V Pedone C Pedone E Saviano M 《Journal of bacteriology》2003,185(14):4285-4289
We report a crystallographic and computational analysis of two mutant forms of the Alicyclobacillus acidocaldarius thioredoxin (BacTrx) done in order to evaluate the contribution of two specific amino acids to the thermostability of BacTrx. Our results suggest that the thermostability of BacTrx may be modulated by mutations affecting the overall electrostatic energy of the protein. 相似文献
964.
Gianni D Zambrano N Bimonte M Minopoli G Mercken L Talamo F Scaloni A Russo T 《The Journal of biological chemistry》2003,278(11):9290-9297
965.
Coeliac disease (CD) is one of the most frequent chronic diseases in childhood. The clinical spectrum has changed; in addition to the classical gastrointestinal form, other clinical manifestations have been described, such as hypogonadism and the consequent delay in onset of puberty. Recent studies reported not only a significantly retarded menarche in untreated CD girls as compared with girls following a gluten-free diet, but also in treated CD a negative effect on pregnancy, resulting in lower birth weight and shorter duration of pregnancy. In boys, there is a reduced serum level of dihydrotestosterone and an increased serum level of luteinizing hormone, an abnormality pattern suggesting androgen resistance. The pathogenesis of CD-related reproductive disorders is still unclear. Some hypotheses may be tried; for example, in CD there is a high level of autoantibodies directed against self-antigens, so there could be antibodies directed against hormones or organs critical for pubertal development. Moreover, in CD there could be a selective malabsorption of micronutrients essential for the metabolism of carrier or receptor proteins for sex hormones. 相似文献
966.
Hormonal stimulation and oocyte maturational competence in prepuberal Mediterranean Italian buffaloes (Bubalus bubalis) 总被引:1,自引:0,他引:1
Presicce GA Senatore EM De Santis G Stecco R Terzano GM Borghese A De Mauro GJ 《Theriogenology》2002,57(7):1877-1884
The objective of this study was to determine the best combined hormonal treatment to utilize in order to obtain a high number of good quality in vivo and in vitro matured oocytes from prepuberal Mediterranean Italian buffalo calves (Bubalus bubalis). Transvaginal ultrasound follicular aspiration was employed to recover oocytes from antral follicles. Fifteen barn housed buffalo calves, between 5 and 9 months of age were used in this study and randomly divided into control (Group A) and treated groups. A commercially available preparation of 2000 IU eCG was administered to animals in the treatment groups, followed by 2000 IU of hCG given either 12 h (Group B), or 24 h (Group C) before ovum pick up (OPU). From the time of administration of eCG treatments, the best timing for hCG administration before OPU was determined and integrated with the administration of 500 IU of FSH-LH in a decreasing dosage protocol over 4 days (Group D). Expanded cumulus oocyte complexes (COCs) recovered from all groups were immediately fixed for later aceto-orcein staining. All other COCs were processed for in vitro maturation using standard procedures and then fixed and stained for assessment of nuclear maturation. Collectively, hormonal stimulation did not increase the number of ovarian antral follicles available compared to the control group (P > 0.05), but did result in higher output of medium (Group B: 9.8 +/- 7.1; Group C: 3.4 +/- 6.7; Group D: 15.6 +/- 4.9 versus Group A: 1.6 +/- 2.2) and large follicles (Group B: 44.8 +/- 22.9; Group C: 8.7 +/- 6.1; Group D: 70.2 +/- 10 versus Group A: 6.1 +/- 6.3). Administration of hCG 12 h before follicle aspiration proved to be the best strategy to obtain high numbers of immature and mature oocytes from antral follicles (P < 0.05; Group B: 70.8 +/- 12 and Group D: 82 +/- 12.6 versus Group A: 43.6 +/- 13.9 and Group C: 27.2 +/- 13.9). A significantly higher number of expanded COCs was obtained from hormonally stimulated groups compared to the control group (P < 0.05; Group B: 28.7 +/- 16.8, Group C: 16.3 +/- 5.9 and Group D: 27.1 +/- 16.9 versus Group A: 6.2 +/- 6). A higher oocyte maturational competence (P < 0.05) was found in Groups A, B and D (80.8 +/- 7.9, 87.5 +/- 8.2, and 86.5 +/- 4.3, respectively) compared to Group C (60 +/- 26.2). In conclusion, in prepuberal buffalo calves combined gonadotrophin stimulation protocols yielded higher numbers of medium to large size follicles compared to a control group. A high number of good quality oocytes were recovered by transvaginal ultrasound follicle aspiration, and a high rate of metaphase II progression was reached after in vivo and in vitro maturation. 相似文献
967.
An N-terminal polypeptide (XVAX2-P104) of the XVAX2 protein, which is involved in controlling the dorsoventral patterning of the retina in Xenopus laevis, was expressed and purified as a Histagged fusion protein (pHis-XVAX2-P104), and it was employed to generate an anti-XVAX2 antibody in New Zealand white rabbits. ELISA analysis shows that the titer of the antibody is as high as approximately 1:100,000. The antibody could specifically recognize the full-length XVAX2 protein in extracts of Xenopus embryos, as determined by Western Blotting. 相似文献
968.
Mitova M Tommonaro G De Rosa S 《Zeitschrift für Naturforschung. C, Journal of biosciences》2003,58(9-10):740-745
A new cyclotetrapeptide 1, together with three known cyclopeptides were isolated from the exo-cellular extract of Pseudomonas sp. a bacterium associated with the sponge Ircinia muscarum. The structure of 1 was suggested on the basis of spectroscopic analytical data and chemical degradation. 相似文献
969.
Interleukin-10 deficiency increases atherosclerosis,thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice 总被引:9,自引:0,他引:9
Caligiuri G Rudling M Ollivier V Jacob MP Michel JB Hansson GK Nicoletti A 《Molecular medicine (Cambridge, Mass.)》2003,9(1-2):10-17
Interleukin (IL)-10 is an anti-inflammatory cytokine that may play a protective role in atherosclerosis. The aim of this study was to assess the effect of IL-10 deficiency in the apolipoprotein E knockout mouse. Apolipoprotein E deficient (E-/-) and IL-10 deficient (-/-) mice were crossed to generate E-/- x IL-10-/- double knockout mice. By 16 wk, cholesterol and triglycerides were similar in double and single knockouts but the lack of IL-10 led to increased low-density lipoprotein cholesterol whereas very-low-density lipoprotein was reduced. In parallel, T-helper 1 responses and lesion size were dramatically increased in double knockout compared with E-/- controls. At 48 wk, matrix metalloproteinases and tissue factor activities were increased in lesions of double-knockout mice. Furthermore, markers of systemic coagulation were increased, and vascular thrombosis in response to i.v. thrombin occurred more frequently in E-/- x IL-10-/- than in E-/- mice. Our findings suggest that IL-10 deficiency plays a deleterious role in atherosclerosis. The early phase of lesion development was increased, and the proteolytic and procoagulant activity was elevated in advanced lesions. These data show that IL-10 may reduce atherogenesis and improve the stability of plaques. 相似文献
970.
De Rosa S De Caro S Iodice C Tommonaro G Stefanov K Popov S 《Journal of biotechnology》2003,100(2):119-125
We have established primary cell culture of the marine demosponge Dysidea avara and Suberites domuncula. Microbial contamination was controlled by the use of a pool of antibiotics confirming the goodness of this procedure. Effect of pH, temperature and light was studied to establish the better growth conditions. The comparison of lipid composition of sponge and cells suggested a series of experiments to optimise the medium. A glucose dose-dependent experiment showed that the ideal glucose concentration is 1 g l(-1). Supplementing the medium with unsaturated fatty acid and retinol, no promotion of growth was observed, but the compounds were totally metabolised by cells. Increments from 70 to 160% in the number of cells were observed, supplementing the medium with different concentration of cholesterol. These results suggest that the analysis of the chemical composition of sponge and cells give indication on the composition of the nutrient media. 相似文献