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   1271篇
  免费   123篇
  国内免费   2篇
  1396篇
  2023年   10篇
  2022年   12篇
  2021年   29篇
  2020年   22篇
  2019年   33篇
  2018年   37篇
  2017年   46篇
  2016年   45篇
  2015年   50篇
  2014年   57篇
  2013年   94篇
  2012年   99篇
  2011年   96篇
  2010年   67篇
  2009年   43篇
  2008年   71篇
  2007年   64篇
  2006年   50篇
  2005年   34篇
  2004年   37篇
  2003年   32篇
  2002年   42篇
  2001年   29篇
  2000年   34篇
  1999年   26篇
  1998年   17篇
  1997年   9篇
  1996年   13篇
  1995年   11篇
  1994年   10篇
  1992年   13篇
  1991年   10篇
  1990年   12篇
  1989年   13篇
  1988年   8篇
  1987年   9篇
  1986年   11篇
  1985年   12篇
  1984年   11篇
  1983年   7篇
  1982年   6篇
  1981年   7篇
  1979年   8篇
  1978年   4篇
  1977年   7篇
  1974年   4篇
  1973年   6篇
  1971年   5篇
  1968年   5篇
  1967年   3篇
排序方式: 共有1396条查询结果,搜索用时 7 毫秒
141.
In rodents, the formation of ovarian follicles occurs after birth. In recent years, several factors required for follicular assembly and the growth of the newly formed follicles have been identified. We now describe a novel gene, Fxna, identified by differential display in the neonatal rat ovary. Fxna encodes an mRNA of 5.4 kb, and a protein of 898 amino acids. Fxna is a transmembrane metallopeptidase from family M28, localized to the endoplasmic reticulum. In the ovary, Fxna mRNA is expressed in granulosa cells; its abundance is maximal 48 hours after birth, i.e. during the initiation of follicular assembly. Reducing Fxna mRNA levels via lentiviral-mediated delivery of short hairpin RNAs to neonatal ovaries resulted in substantial loss of primordial, primary and secondary follicles, and structural disorganization of the ovary, with many abnormal follicles containing more than one oocyte and clusters of somatic cells not associated with any oocytes. These abnormalities were not attributable to either increased apoptosis or decreased proliferation of granulosa cells. The results indicate that Fxna is required for the organization of somatic cells and oocytes into discrete follicular structures. As an endoplasmic reticulum-bound peptidase, Fxna may facilitate follicular organization by processing precursor proteins required for intraovarian cell-to-cell communication.  相似文献   
142.
The rapid tissue necrosis (RTN) is a common disease of both wild and captive stony corals, which causes a fast tissue degradation (peeling) and death of the colony. Here we report the results of an investigation carried out on the stony coral Pocillopora damicornis, affected by an RTN-like disease. Total abundance of prokaryotes in tissue samples, determined by epifluorescence microscopy, was significantly higher in diseased than in healthy corals, as well as bacterial counts on MB2216 agar plates. Further experiments performed by fluorescent in situ hybridization using a 16S rDNA Vibrio-specific probe showed that vibrios were significantly more abundant in diseased than in healthy corals. Accordingly, bacterial counts on TCBS agar plates were higher in diseased than in healthy tissues. 16S rDNA sequencing identified as Vibrio colonies from diseased tissues only. Cultivated vibrios were dominated by a single ribotype, which displayed 99% of similarity with Vibrio harveyi strain LB4. Bacterial ribotype richness, assessed by terminal-restriction fragment length polymorphism analysis of the 16S rDNA, was significantly higher in diseased than in healthy corals. Using an in silico software, we estimated that a single terminal restriction fragment, putatively assigned to a Vibrio sp., accounted for > 15% and < 5% of the total bacterial assemblage, in diseased and healthy corals respectively. These results let us hypothesize that the RTN in stony corals can be an infectious disease associated to the presence of Vibrio harveyi. However, further studies are needed to validate the microbial origin of this pathology.  相似文献   
143.
Corynebacterium diphtheriae, the aetiologic agent of diphtheria, also represents a global medical challenge because of the existence of invasive strains as causative agents of systemic infections. Although tellurite (TeO32-) is toxic to most microorganisms, TeO32--resistant bacteria, including C. diphtheriae, exist in nature. The presence of TeO32--resistance (TeR) determinants in pathogenic bacteria might provide selective advantages in the natural environment. In the present study, we investigated the role of the putative TeR determinant (CDCE8392_813gene) in the virulence attributes of diphtheria bacilli. The disruption of CDCE8392_0813 gene expression in the LDCIC-L1 mutant increased susceptibility to TeO32- and reactive oxygen species (hydrogen peroxide), but not to other antimicrobial agents. The LDCIC-L1 mutant also showed a decrease in both the lethality of Caenorhabditis elegans and the survival inside of human epithelial cells compared to wild-type strain. Conversely, the haemagglutinating activity and adherence to and formation of biofilms on different abiotic surfaces were not regulated through the CDCE8392_0813 gene. In conclusion, the CDCE8392_813 gene contributes to the TeR and pathogenic potential of C. diphtheriae.  相似文献   
144.
Human plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor with a metastable active conformation. The lifespan of the active form of PAI-1 is modulated via interaction with the plasma protein, vitronectin, and various metal ions. These metal ions fall into two categories: Type I metals, including calcium, magnesium, and manganese, stabilize PAI-1 in the absence of vitronectin, whereas Type II metals, including cobalt, copper, and nickel, destabilize PAI-1 in the absence of vitronectin, but stabilize PAI-1 in its presence. To provide a mechanistic basis for understanding the unusual modulation of PAI-1 structure and activity, the binding characteristics and conformational effects of these two types of metals were further evaluated. Steady-state binding measurements using surface plasmon resonance indicated that both active and latent PAI-1 exhibit a dissociation constant in the low micromolar range for binding to immobilized nickel. Stopped-flow measurements of approach-to-equilibrium changes in intrinsic protein fluorescence indicated that the Type I and Type II metals bind in different modes that induce distinct conformational effects on PAI-1. Changes in the observed rate constants with varying concentrations of metal allowed accurate determination of binding affinities for cobalt, nickel, and copper, yielding dissociation constants of ~40, 30, and 0.09 μM, respectively. Competition experiments that tested effects on PAI-1 stability were consistent with these measurements of affinity and indicate that copper binds tightly to PAI-1.  相似文献   
145.

Background  

Two component systems (TCS) are signal transduction pathways which typically consist of a sensor histidine kinase (HK) and a response regulator (RR). In this study, we have analyzed the evolution of TCS of the OmpR/IIIA family in Lactobacillaceae and Leuconostocaceae, two families belonging to the group of lactic acid bacteria (LAB). LAB colonize nutrient-rich environments such as foodstuffs, plant materials and the gastrointestinal tract of animals thus driving the study of this group of both basic and applied interest.  相似文献   
146.
147.
148.
This paper deals with the fertility pattern of the El Ejido population, an agricultural Spanish community characterised by the rapid development of its modern agrarian economy. Consequently, the arrival of immigrants has sharply increased throughout the second half of the twentieth century, with important demographic consequences as well as reproductive changes. The analyses of the age-specific fertility rate (fx) and the total fertility rate (TFR) were used in order to describe the reproductive pattern of this population in 2000. The main characteristics were the following: a) Regarding the temporal change, an important decrease of fx has been observed in all age groups for the last twenty years, as a consequence of progressive birth control. However, the reproductive pattern has kept almost invariable and has been characterised by a maximum fertility at age group of 25-29 years old. b) Regarding the general Spanish fertility, the comparison of fx in both populations suggests a younger maternity in the agricultural population than in the national, the maximum fertility delayed to the 30-34 age group. c) Moreover, the El Ejido population showed a clear higher offspring per woman (TFR = 1.42) than the national (TFR = 1.24), according to the agrarian character of the El Ejido population. d) Finally, this greater reproductive level of El Ejido is also due to the arrival of women at fertile age, who come mainly from Africa, and above all from Morocco.  相似文献   
149.
Neonatal mortality during the first week of life, corresponding to the years 1975-1998, was studied in Spain. The first week of life is the time in which the highest number of deaths occur. The temporal decrease of the neonatal mortality rate (NMR) was modelled according to log10(NMR+1)= 2.784 - 0.023 per year. This decline cannot be explained by an increase in the mean birth weight (MBW=23440.835 - 10.107 g per year). From the most frequent of the causes of death to the least were: congenital anomalies, preterm born or low birth weight, respiratory problems, pregnancy difficulties, hypoxaemia/asphyxia, delivery difficulties and infectious diseases. This sequence changed when the specific age at death was considered. The NMR descended evenly for both sexes for the causes indicated above, except for preterm born or low birth weight, in which the male mortality decrease was greater since its rate was more elevated at the beginning of the period studied. For all the causes listed, NMR was more elevated both in urban areas and for males. Early neonatal mortality (first 24 hours) was higher for pregnancy difficulties, preterm born or low birth weight, congenital anomalies and hypoxaemia/asphyxia.  相似文献   
150.
We have previously demonstrated that introgression of PcINO1 gene from Porteresia coarctata (Roxb.) Tateoka, coding for a novel salt-tolerant L-myo-inositol 1-phosphate synthase (MIPS) protein, confers salt tolerance to transgenic tobacco plants (Majee, M., Maitra, S., Dastidar, K.G., Pattnaik, S., Chatterjee, A., Hait, N.C., Das, K.P. and Majumder, A.L. (2004) A novel salt-tolerant L-myo-inositol-1-phosphate synthase from Porteresia coarctata (Roxb.) Tateoka, a halophytic wild rice: molecular cloning, bacterial overexpression, characterization, and functional introgression into tobacco-conferring salt-tolerance phenotype. J. Biol. Chem. 279, 28539-28552). In this communication we have shown that functional introgression of the PcINO1 gene confers salt-tolerance to evolutionary diverse organisms from prokaryotes to eukaryotes including crop plants albeit to a variable extent. A direct correlation between unabated increased synthesis of inositol under salinity stress by the PcINO1 gene product and salt tolerance has been demonstrated for all the systems pointing towards the universality of the application across evolutionary divergent taxa.  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