全文获取类型
收费全文 | 615篇 |
免费 | 62篇 |
出版年
2023年 | 7篇 |
2022年 | 8篇 |
2021年 | 16篇 |
2020年 | 15篇 |
2019年 | 19篇 |
2018年 | 13篇 |
2017年 | 15篇 |
2016年 | 31篇 |
2015年 | 26篇 |
2014年 | 27篇 |
2013年 | 34篇 |
2012年 | 46篇 |
2011年 | 51篇 |
2010年 | 33篇 |
2009年 | 20篇 |
2008年 | 44篇 |
2007年 | 40篇 |
2006年 | 36篇 |
2005年 | 35篇 |
2004年 | 31篇 |
2003年 | 22篇 |
2002年 | 27篇 |
2001年 | 13篇 |
2000年 | 10篇 |
1999年 | 13篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1974年 | 1篇 |
1968年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有677条查询结果,搜索用时 15 毫秒
41.
Morelli L Llovera R Gonzalez SA Affranchino JL Prelli F Frangione B Ghiso J Castano EM 《The Journal of biological chemistry》2003,278(26):23221-23226
Inherited amino acid substitutions at position 21, 22, or 23 of amyloid beta (Abeta) lead to presenile dementia or stroke. Insulin-degrading enzyme (IDE) can hydrolyze Abeta wild type, yet whether IDE is capable of degrading Abeta bearing pathogenic substitutions is not known. We studied the degradation of all of the published Abeta genetic variants by recombinant rat IDE (rIDE). Monomeric Abeta wild type, Flemish (A21G), Italian (E22K), and Iowa (D23N) variants were readily degraded by rIDE with a similar efficiency. However, proteolysis of Abeta Dutch (E22Q) and Arctic (E22G) was significantly lower as compared with Abeta wild type and the rest of the mutant peptides. In the case of Abeta Dutch, inefficient proteolysis was related to a high content of beta structure as assessed by circular dichroism. All of the Abeta variants were cleaved at Glu3-Phe4 and Phe4-Arg5 in addition to the previously described major sites within positions 13-15 and 18-21. SDS-stable Abeta dimers were highly resistant to proteolysis by rIDE regardless of the variant, suggesting that IDE recognizes a conformation that is available for interaction only in monomeric Abeta. These results raise the possibility that upregulation of IDE may promote the clearance of soluble Abeta in hereditary forms of Abeta diseases. 相似文献
42.
From April 1984 to March 1985, a Trypanosoma lewisi prevalence of 21.7% was found in 429 Rattus norvegicus trapped in Belo Horizonte, State of Minas Gerais, Brazil. The infection rates were higher in male and young rats and could be attributed to ecological and behavioral factors. T. lewisi was observed in rats measuring between 60 and 250 mm. Data about monthly T. lewisi infections throughout the year are presented for the first time in Brazil, with the highest prevalences observed in the warm-rainy season (October to March). 相似文献
43.
44.
45.
Hunter RP Koch DE Mutlow A Isaza R 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,793(2):351-355
This method is the first analytical method for the detection and quantitation of carfentanil and naltrexone at clinically relevant concentrations using liquid chromatography-mass spectrometry. Samples were alkalinized with 100 microl of 1 M NaOH and extracted 2x with 2 ml of toluene. The extractions were combined and dried under N(2) at 40 degrees C in a H(2)O bath. Chromatography was performed using a Zirchrom PBD column and a mobile phase of 30:70 acetonitrile/10 mM ammonium acetate and 0.1 mM citrate (pH=4.4) at a flow rate of 0.3 ml/min. The lower limit of quantitation was 8.5 pg/ml for carfentanil and 0.21 ng/ml for naltrexone. 相似文献
46.
Schizosaccharomyces pombe Rho1p regulates (1,3)beta-d-glucan synthesis and is required for cell integrity maintenance and actin cytoskeleton organization, but nothing is known about the regulation of this protein. At least nine different S. pombe genes code for proteins predicted to act as Rho GTPase-activating proteins (GAPs). The results shown in this paper demonstrate that the protein encoded by the gene named rga5+ is a GAP specific for Rho1p. rga5+ overexpression is lethal and causes morphological alterations similar to those reported for Rho1p inactivation. rga5+ deletion is not lethal and causes a mild general increase in cell wall biosynthesis and morphological alterations when cells are grown at 37 degrees C. Upon mild overexpression, Rga5p localizes to growth areas and possesses both in vivo and in vitro GAP activity specific for Rho1p. Overexpression of rho1+ in rga5Delta cells is lethal, with a morphological phenotype resembling that of the overexpression of the constitutively active allele rho1G15V. In addition (1,3)beta-d-glucan synthase activity, regulated by Rho1p, is increased in rga5Delta cells and decreased in rga5-overexpressing cells. Moreover, the increase in (1,3)beta-d-glucan synthase activity caused by rho1+ overexpression is considerably higher in rga5Delta than in wild-type cells. Genetic interactions suggest that Rga5p is also important for the regulation of the other known Rho1p effectors, Pck1p and Pck2p. 相似文献
47.
Palatnik JF Tognetti VB Poli HO Rodríguez RE Blanco N Gattuso M Hajirezaei MR Sonnewald U Valle EM Carrillo N 《The Plant journal : for cell and molecular biology》2003,35(3):332-341
Ferredoxin-NADP(H) reductase (FNR) catalyses the final step of the photosynthetic electron transport in chloroplasts. Using an antisense RNA strategy to reduce expression of this flavoenzyme in transgenic tobacco plants, it has been demonstrated that FNR mediates a rate-limiting step of photosynthesis under both limiting and saturating light conditions. Here, we show that these FNR-deficient plants are abnormally prone to photo-oxidative injury. When grown under autotrophic conditions for 3 weeks, specimens with 20-40% extant reductase undergo leaf bleaching, lipid peroxidation and membrane damage. The magnitude of the effect was proportional to the light intensity and to the extent of FNR depletion, and was accompanied by morphological changes involving accumulation of aberrant plastids with defective thylakoid stacking. Damage was initially confined to chloroplast membranes, whereas Rubisco and other stromal proteins began to decline only after several weeks of autotrophic growth, paralleled by partial recovery of NADPH levels. Exposure of the transgenic plants to moderately high irradiation resulted in rapid loss of photosynthetic capacity and accumulation of singlet oxygen in leaves. The collected results suggest that the extensive photo-oxidative damage sustained by plants impaired in FNR expression was caused by singlet oxygen building up to toxic levels in these tissues, as a direct consequence of the over-reduction of the electron transport chain in FNR-deficient chloroplasts. 相似文献
48.
Koo H Rosalen PL Cury JA Ambrosano GM Murata RM Yatsuda R Ikegaki M Alencar SM Park YK 《Current microbiology》2000,41(3):192-196
The effects of a new variety of propolis, from Northeastern Brazil (BA), on growth of mutans streptococci, cell adherence,
and water-insoluble glucan (WIG) synthesis were evaluated. Propolis from Southeastern (MG) and Southern (RS) Brazil were also
tested as an extension of our previous work. Ethanolic extracts of propolis (EEP) were prepared and analyzed by reversed-phase
HPLC. For the antibacterial activity assays, minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations
(MBC) of EEPs against Streptococcus mutans, S. sobrinus, and S. cricetus were determined. Cell adherence of S. mutans and S. sobrinus to a glass surface was measured spectrophotometrically at 550 nm. WIG synthesized from sucrose by glucosyltransferase (Gtf)
was extracted and quantified by the phenol-sulfuric method. The HPLC profile of the new variety of propolis was entirely different
from Southeastern and Southern propolis. Neither flavonoid aglycones nor p-coumaric acid were detected in EEP BA. All EEPs demonstrated biological activities against mutans streptococci; EEP BA showed
the highest potency in all in vitro parameters evaluated in this study. The ranges of MIC values were 50 (EEP BA)–400 μg/ml
(MG), for S. mutans; and 25 (BA)–400 μg/ml (MG), for S. sobrinus and S. cricetus. The bactericidal concentration of EEPs was four to eight times the MIC values. The adherence of S. mutans and S. sobrinus cells and WIG synthesis were markedly inhibited by EEPs, demonstrating significant inhibition at all concentrations compared
with the control (80% ethanol) (p < 0.05). EEP BA showed 80% inhibition of cell adherence and WIG synthesis at concentrations as low as 12.5 and 7.8 μg/ml, respectively.
The results show that the new variety of propolis was exceptionally effective in all in vitro parameters tested against mutans
streptococci; biological effects of propolis are likely not to be due solely to flavonoids and (hydroxy)cinnamic acid derivatives.
Received: 14 February 2000 / Accepted: 8 May 2000 相似文献
49.
Patricia Garcia de Olalla Ema Molas María Jesús Barberà Silvia Martín Encarnació Arellano Mercè Gosch Pilar Saladie Teresa Carbonell Hernando Knobel Elia Diez Joan A Caylà 《PloS one》2015,10(4)
Background
An estimated 30% of HIV cases in the European Union are not aware of their serological status. This study aimed to assess the effectiveness of a pilot HIV partner notification program.Methods
HIV cases diagnosed between January 2012 and June 2013 at two healthcare settings in Barcelona were invited to participate in a prospective survey. We identified process and outcome measures to evaluate this partner notification program, including the number of partners identified per interviewed index case, the proportion of partners tested for HIV as a result of the partner notification, and the proportion of new HIV diagnoses among their sex or needle-sharing partners.Results
Of the 125 index cases contacted, 108 (86.4%) agreed to provide information about partners. A total of 199 sexual partners were identified (1.8 partners per interviewed index case). HIV outcome was already known for 58 partners (70.7% were known to be HIV-positive), 141 partners were tested as result of partner notification, and 26 were newly diagnosed with HIV. The case-finding effectiveness of the program was 18.4%.Conclusion
This pilot program provides evidence of the effectiveness of a partner notification program implemented in healthcare settings. This active partner notification program was feasible, acceptable to the user, and identified a high proportion of HIV-infected patients previously unaware of their status. 相似文献50.
Aili Guo Nigel A. Daniels Jean Thuma Kelly D. McCall Ramiro Malgor Frank L. Schwartz 《PloS one》2015,10(1)