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   2502篇
  免费   210篇
  2023年   12篇
  2022年   25篇
  2021年   45篇
  2020年   37篇
  2019年   34篇
  2018年   44篇
  2017年   29篇
  2016年   51篇
  2015年   108篇
  2014年   117篇
  2013年   145篇
  2012年   180篇
  2011年   164篇
  2010年   121篇
  2009年   105篇
  2008年   141篇
  2007年   141篇
  2006年   134篇
  2005年   122篇
  2004年   126篇
  2003年   115篇
  2002年   99篇
  2001年   49篇
  2000年   44篇
  1999年   46篇
  1998年   34篇
  1997年   29篇
  1996年   19篇
  1995年   22篇
  1994年   17篇
  1993年   12篇
  1992年   29篇
  1991年   26篇
  1990年   32篇
  1989年   29篇
  1988年   35篇
  1987年   37篇
  1986年   20篇
  1985年   21篇
  1984年   14篇
  1983年   13篇
  1982年   11篇
  1981年   7篇
  1980年   6篇
  1979年   16篇
  1978年   7篇
  1977年   10篇
  1976年   8篇
  1971年   2篇
  1970年   3篇
排序方式: 共有2712条查询结果,搜索用时 15 毫秒
961.
Dendritic cells (DCs) are professional APCs that have a unique capacity to initiate primary immune responses, including tolerogenic responses. We have genetically engineered bone marrow-derived DCs to express the immunosuppressive cytokine IL-10 and tested the ability of these cells to control experimental asthma. A single intratracheal injection of OVA-pulsed IL-10-transduced DCs (OVA-IL-10-DCs) to naive mice before OVA sensitization and challenge prevented all of the cardinal features of airway allergy, namely, eosinophilic airway inflammation, airway hyperreactivity, and production of mucus, Ag-specific Igs, and IL-4. OVA-IL-10-DCs also reversed established experimental asthma and had long-lasting and Ag-specific effects. We furthermore showed, by using IL-10-deficient mice, that host IL-10 is required for mediating the immunomodulatory effects of OVA-IL-10-DCs and demonstrated a significant increase in the percentage of OVA-specific CD4(+)CD25(+)Foxp3(+)IL-10(+) regulatory T cells in the mediastinal lymph nodes of OVA-IL-10-DC-injected mice. Finally, adoptive transfer of CD4(+) mediastinal lymph node T cells from mice injected with OVA-IL-10-DCs protected OVA-sensitized recipients from airway eosinophilia upon OVA provocation. Our study describes a promising strategy to induce long-lasting Ag-specific tolerance in airway allergy.  相似文献   
962.
Nicotinamide phosphoribosyl transferase (Nampt)/pre-B cell colony-enhancing factor (PBEF)/visfatin is a protein displaying multiple functional properties. Originally described as a cytokine-like protein able to regulate B cell development, apoptosis, and glucose metabolism, this protein also plays an important role in NAD biosynthesis. To gain insight into its physiological role, we have generated a mouse strain expressing a conditional Nampt allele. Lack of Nampt expression strongly affects development of both T and B lymphocytes. Analysis of hemizygous cells and in vitro cell lines expressing distinct levels of Nampt illustrates the critical role of this protein in regulating intracellular NAD levels. Consequently, a clear relationship was found between intracellular Nampt levels and cell death in response to the genotoxic agent MNNG (N-methyl-N'-nitro-N-nitrosoguanidine), confirming that this enzyme represents a key regulator of cell sensitivity to NAD-consuming stress secondary to poly(ADP-ribose) polymerases overactivation. By using mutant forms of this protein and a well-characterized pharmacological inhibitor (FK866), we unequivocally demonstrate that the ability of the Nampt to regulate cell viability during genotoxic stress requires its enzymatic activity. Collectively, these data demonstrate that Nampt participates in cellular resistance to genotoxic/oxidative stress, and it may confer to cells of the immune system the ability to survive during stressful situations such as inflammation.  相似文献   
963.
964.
The pentapeptide repeat is a recently discovered protein fold. Mycobacterium tuberculosis MfpA is a founding member of the pentapeptide repeat protein (PRP) family that confers resistance to the antibiotic fluoroquinolone by binding to DNA gyrase and inhibiting its activity. The size, shape, and surface potential of MfpA mimics duplex DNA. As an initial step in a comprehensive biophysical analysis of the role of PRPs in the regulation of cellular topoisomerase activity and conferring antibiotic resistance, we have explored the solution structure and refolding of MfpA by fluorescence spectroscopy, CD, and analytical centrifugation. A unique CD spectrum for the pentapeptide repeat fold is described. This spectrum reveals a native structure whose beta-strands and turns within the right-handed quadrilateral beta-helix that define the PRP fold differ from canonical secondary structure types. MfpA refolded from urea or guanidium by dialysis or dilution forms stable aggregates of monomers whose secondary and tertiary structure are not native. In contrast, MfpA refolded using a novel "time-dependent renaturation" protocol yields protein with native secondary, tertiary, and quaternary structure. The generality of "time-dependent renaturation" to other proteins and denaturation methods is discussed.  相似文献   
965.
966.
We have investigated the photosynthetic properties of Acaryochloris marina, a cyanobacterium distinguished by having a high level of chlorophyll d, which has its absorption bands shifted to the red when compared with chlorophyll a. Despite this unusual pigment content, the overall rate and thermodynamics of the photosynthetic electron flow are similar to those of chlorophyll a-containing species. The midpoint potential of both cytochrome f and the primary electron donor of photosystem I (P(740)) were found to be unchanged with respect to those prevailing in organisms having chlorophyll a, being 345 and 425 mV, respectively. Thus, contrary to previous reports (Hu, Q., Miyashita, H., Iwasaki, I. I., Kurano, N., Miyachi, S., Iwaki, M., and Itoh, S. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 13319-13323), the midpoint potential of the electron donor P(740) has not been tuned to compensate for the decrease in excitonic energy in A. marina and to maintain the reducing power of photosystem I. We argue that this is a weaker constraint on the engineering of the oxygenic photosynthetic electron transfer chain than preserving the driving force for plastoquinol oxidation by P(740), via the cytochrome b(6)f complex. We further show that there is no restriction in the diffusion of the soluble electron carrier between cytochrome b(6)f and photosystem I in A. marina, at variance with plants. This difference probably reflects the simplified ultrastructure of the thylakoids of this organism, where no segregation into grana and stroma lamellae is observed. Nevertheless, chlorophyll fluorescence measurements suggest that there is energy transfer between adjacent photosystem II complexes but not from photosystem II to photosystem I, indicating spatial separation between the two photosystems.  相似文献   
967.
We constructed and characterized the first large-insert DNA BAC library for Arabidopsis halleri, a close relative of Arabidopsis thaliana. Double size selection of high molecular weight DNA was performed to increase the average insert size. The BAC library consists of 6128 clones of which 87% have an insert size above 125 kb. Organellar DNA contamination is estimated to 1.4%. The coverage of the library is equivalent to 4.5 times the haploid genome (250 Mb), indicating the library is suitable for almost any application. We explored the possibility of generating a physical map of A. halleri using the high conserved synteny existing between this species and A. thaliana. A set of unigenes separated by 50 kb in a 850 kb region of A. thaliana chromosome II was used to probe the library. The A. halleri BAC clones isolated with these probes were grouped into two contigs. Analysis of BAC-end sequences revealed that the two A. halleri genomic contigs were highly colinear with the A. thaliana genome. Therefore, the exploitation of the conserved synteny existing between the two species will greatly facilitate the construction of a raw full physical map of A. halleri.  相似文献   
968.
Suitable sleeping sites as potentially restricted resources are suggested to shape sociality in primates. We investigated sleeping site ecology of a rain-forest dwelling sportive lemur in eastern Madagascar for the first time. Using radiotelemetry, we characterized the type, quality and usage of sleeping sites as well as social sleeping habits of 11 focal individuals of the weasel sportive lemur (Lepilemur mustelinus) during the dry and the onset of the rainy season. Morphometric measurements provided additional information. The sexes showed an unusual sexual dimorphism for primates. Males and females did not differ in body length, but females surpassed males in body mass suggesting female dominance. Both sexes used dense vegetation and holes in hollow trees high above the ground as shelters for sleeping during the day. No sex difference in the quality of tree holes was found, but focal individuals used tree holes more often than open sleeping sites in dense vegetation. Both sexes showed high sleeping site fidelity limited to two to six different sites that they used primarily solitarily. The results imply that suitable sleeping sites are limited and survival of this species will strongly depend on the availability of mature rain forests with suitable hollow trees. Furthermore, these findings provide evidence of a solitary sleeping and ranging system in this rain-forest dwelling sportive lemur with suitable sleeping sites as defendable resources.  相似文献   
969.

Background  

Evidence of multiple genetic criteria of mate choice is accumulating in numerous taxa. In many species, females have been shown to pair with genetically dissimilar mates or with extra-pair partners that are more genetically compatible than their social mates, thereby increasing their offsprings' heterozygosity which often correlates with offspring fitness. While most studies have focused on genetically promiscuous species, few studies have addressed genetically monogamous species, in which mate choice tends to be mutual.  相似文献   
970.
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