首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   3777篇
  免费   286篇
  国内免费   27篇
  4090篇
  2024年   6篇
  2023年   30篇
  2022年   28篇
  2021年   89篇
  2020年   89篇
  2019年   94篇
  2018年   165篇
  2017年   154篇
  2016年   171篇
  2015年   254篇
  2014年   250篇
  2013年   299篇
  2012年   362篇
  2011年   330篇
  2010年   193篇
  2009年   155篇
  2008年   240篇
  2007年   197篇
  2006年   160篇
  2005年   165篇
  2004年   141篇
  2003年   127篇
  2002年   103篇
  2001年   40篇
  2000年   34篇
  1999年   33篇
  1998年   10篇
  1997年   15篇
  1996年   17篇
  1995年   10篇
  1994年   10篇
  1993年   10篇
  1992年   11篇
  1991年   14篇
  1990年   8篇
  1989年   9篇
  1988年   6篇
  1987年   7篇
  1986年   4篇
  1985年   8篇
  1984年   6篇
  1981年   2篇
  1977年   4篇
  1976年   3篇
  1975年   5篇
  1974年   4篇
  1973年   3篇
  1969年   2篇
  1967年   3篇
  1965年   2篇
排序方式: 共有4090条查询结果,搜索用时 15 毫秒
1.
A promising producer of bioactive compounds isolated from a Brazilian tropical soil was tested for its range of antimicrobial activities. Strain 606, classified as Streptomyces sp., could not be identified up to species level, suggesting a possible new taxon. The supernatant and 10 extracts and fractions, obtained by extraction and chromatographic techniques, presented antimicrobial activity using antibiograms. The methanolic fraction was highly active against pathogenic bacteria, phytopathogenic fungi and the human pathogenic yeast Candida albicans. It also possessed high antiviral activity inhibiting the propagation of an acyclovir-resistant herpes simplex virus type 1 strain on HEp-2 cells at non-cytotoxic concentration. The strong cytotoxic effect suggests an antitumour action. This revised version was published online in August 2006 with corrections to the Cover Date.  相似文献   
2.
In this paper, we present a model for the development of connections between muscle afferents and motoneurones in the human spinal cord. The model consists of a limb with six muscles, one motoneurone pool, one pooled (Ia-like) afferent for each muscle and a central programme generator. The weights of the connections between the afferents and the motoneurone pools are adapted during centrally induced movements of the limb. The connections between the afferents and the motoneurone pools adapt in a hebbian way, using only local information present at the synapses. This neural network is tested in two examples of a limb with two degrees of freedom and six muscles. Despite the simplifications, the model predicts the pattern of autogenic and heterogenic monosynaptic reflexes quite realistically.  相似文献   
3.
4.
Probiotics and Antimicrobial Proteins - Beneficial effects of Lactiplantibacillus plantarum strains have been widely reported. Knowing that the effects of probiotic bacteria are strain-dependent,...  相似文献   
5.
From an initial double infection in mice, established by simultaneous and equivalent inocula of bloodstream forms of strains Y and F of Trypanosoma cruzi, two lines were derived by subinoculations: one (W) passaged every week, the other (M) every month. Through biological and biochemical methods only the Y strain was identified at the end of the 10th and 16th passages of line W and only the F strain at the 2nd and 4th passages of line M. The results illustrate strain selection through laboratory manipulation of initially mixed populations of T. cruzi.  相似文献   
6.
7.
Opportunistic infections are an increasingly common problem in hospitals, and the yeast Candida parapsilosis has emerged as an important nosocomial pathogen. The aims of this study were to determine and compare (i) the prevalence rate among C. parapsilosis complex organisms isolated from blood in a public children’s hospital in São Paulo state, (ii) the ability of the complex C. parapsilosis species identified to produce biofilm and (iii) the antifungal susceptibility profiles. Forty-nine (49) specimens of isolated blood yeast were analyzed, previously identified as C. parapsilosis by conventional methods. After the molecular analysis, the isolates were characterized as C. parapsilosis sensu stricto (83.7 %), C. orthopsilosis (10.2 %) and C. metapsilosis (6.1 %). All species were able to form biofilm. The species with the highest biofilm production was C. parapsilosis sensu stricto, followed by C. orthopsilosis and further by C. metapsilosis. All of the strains have demonstrated similar susceptibility to fluconazole, caspofungin, voriconazole, cetoconazole and 5-flucytosine. Only one strain of C. parapsilosis was resistant to amphotericin B. Regarding itraconazole, 66.6 and 43.9 % isolates of C. metapsilosis and C. parapsilosis, respectively, have demonstrated to be susceptible dose-dependent, with one isolate of the latter species resistant to the drug. Candida parapsilosis sensu stricto has demonstrated to be the less susceptible, mainly to amphotericin B, caspofungin and “azoles” such as fluconazole. Therefore, C. metapsilosis and C. orthopsilosis are still involved in a restricted number of infections, but these data have become essential for there are very few studies of these species in Latin America.  相似文献   
8.
The antibiotic resistance phenotype and genotype and the integron type were characterized in 58 Salmonella enterica isolates recovered from Bísaro pigs and wild boars (20 S. Typhimurium, 17 S. Rissen, 14 S. Enteritidis and 7 S. Havana). Most S. Typhimurium isolates (15/20 of Bísaro pigs and wild boars) showed ampicillin, chloramphenicol, streptomycin, tetracycline, sulfonamide, and amoxicillin-clavulanic acid resistances. Of the 17 S. Rissen isolates of both origins, 13 were resistant to ampicillin, tetracycline and trimethoprim-sulfamethoxazole. Among the S. Enteritidis isolates of Bísaro pigs, eight were nalidixic acid-resistant and three were sulfonamide-resistant. The tet(A) or tet(G) genes were detected in most tetracycline-resistant isolates. The intI1 gene was identified in 72.5% of S. enterica isolates in which the conserved region 3' of class 1 integrons (qacEΔ1+sul1) was also amplified, whereas none had the intI2 gene. The dfrA12+orfF+aadA2 gene cassette arrangement was found in the variable region of class 1 integrons in 14 S. Rissen isolates. Fifteen S. Typhimurium isolates had two integrons with variable regions of 1000 and 1200 bp that harbored the aadA2 and blaPSE-1 gene cassettes, respectively. In these isolates the floR and tet(G) genes were also amplified, indicative of the genomic island 1 (SGI1). Salmonella Typhimurium and S. Rissen of animal origin frequently show a multi-antimicrobial resistant phenotype, which may have implications in public health.  相似文献   
9.
Four 5'-substituted fluoro-neplanocin A analogues la-d were designed and synthesized, and the inhibitory activity against SAH was in the following order: NH2 > SH > F, N3, indicating a hydrogen bonding donor is essential for inhibitory activity.  相似文献   
10.
Lee HH 《Molecules and cells》2012,33(3):229-233
Shikimate dehydrogenase (SDH), which catalyses the NADPH-dependent reduction of 3-dehydroshikimate to shikimate in the shikimate pathway, is an attractive target for the development of herbicides and antimicrobial agents. Structural analysis of a SDH from Thermotoga maritima encoded by the Tm0346 gene was performed to facilitate further structural comparisons between the various shikimate dehydrogenases. The crystal structure of SDH from T. maritima was determined at 1.45 Å by molecular replacement. SDH from T. maritima showed a monomeric architecture. The overall structure of SDH from T. maritima comprises the N-terminal α/β sandwich domain for substrate binding and the C-terminal domain for NADP binding. When the T. maritima SDH structure was compared with those of the SDHs from other species, the SDH from T. maritima was in a tightly closed conformation, which should be open for catalysis. Notably, α7 moves toward the active site (∼5 Å), which forces the SDH of T. maritima in a more closed form. Four ammonium sulfate (AMS) ions were identified in the structure. They were located in the active site and appeared to mimic the role of the substrate in terms of the enzyme activity and stability. The new high resolution structural information reported in this study, including the AMS binding sites as a potent inhibitor binding site of SDHs, is expected to supplement the existing structural data and will be useful for structure-based antibacterial discovery against SDHs.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号