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   4107篇
  免费   404篇
  国内免费   1篇
  4512篇
  2023年   26篇
  2022年   72篇
  2021年   132篇
  2020年   112篇
  2019年   113篇
  2018年   136篇
  2017年   131篇
  2016年   187篇
  2015年   235篇
  2014年   285篇
  2013年   288篇
  2012年   337篇
  2011年   283篇
  2010年   201篇
  2009年   161篇
  2008年   191篇
  2007年   197篇
  2006年   174篇
  2005年   149篇
  2004年   146篇
  2003年   114篇
  2002年   92篇
  2001年   65篇
  2000年   66篇
  1999年   75篇
  1998年   47篇
  1997年   23篇
  1996年   28篇
  1995年   21篇
  1994年   14篇
  1993年   29篇
  1992年   32篇
  1991年   29篇
  1990年   34篇
  1989年   33篇
  1988年   24篇
  1987年   32篇
  1986年   17篇
  1985年   22篇
  1984年   22篇
  1983年   17篇
  1982年   8篇
  1980年   7篇
  1979年   9篇
  1978年   11篇
  1976年   7篇
  1975年   16篇
  1974年   7篇
  1971年   8篇
  1969年   9篇
排序方式: 共有4512条查询结果,搜索用时 11 毫秒
61.
Ribosome synthesis in bacteria is linked to RNA polymerase synthesis; both synthesis rates depend upon the values of six parameters: (1) fraction of total ribosomes that is functioning, (2) fraction of total RNA polymerase that is functioning, (3) fraction of functioning RNA polymerase engaged in rRNA synthesis, (4) fraction of total protein that is RNA polymerase protein, (5) peptide chain elongation rate, (6) rRNA chain elongation rate. If these parameters are constant in time, then the numbers of both ribosomes and RNA polymerase molecules increase exponentially. It is shown how the rate constant (fractional increase per unit of time) relates to these parameters and how the kinetics of ribosome and RNA polymerase synthesis respond to a change in any of these parameters.  相似文献   
62.
63.
64.
Interactions between epigenetic readers and histone modifications play a pivotal role in gene expression regulation and aberrations can enact etiopathogenic roles in both developmental and acquired disorders like cancer. Typically, epigenetic interactions are studied by mass spectrometry or chromatin immunoprecipitation sequencing. However, in these methods, spatial information is completely lost. Here, we devise an expansion microscopy based method, termed Expansion Microscopy for Epigenetics or ExEpi, to preserve spatial information and improve resolution. We calculated relative co-localization ratios for two epigenetic readers, lens epithelium derived growth factor (LEDGF) and bromodomain containing protein 4 (BRD4), with marks for heterochromatin (H3K9me3 and H3K27me3) and euchromatin (H3K36me2, H3K36me3 and H3K9/14ac). ExEpi confirmed their preferred epigenetic interactions, showing co-localization for LEDGF with H3K36me3/me2 and for BRD4 with H3K9/14ac. Moreover addition of JQ1, a known BET-inhibitor, abolished BRD4 interaction with H3K9/14ac with an IC50 of 137 nM, indicating ExEpi could serve as a platform for epigenetic drug discovery. Since ExEpi retains spatial information, the nuclear localization of marks and readers was determined, which is one of the main advantages of ExEpi. The heterochromatin mark, H3K9me3, is located in the nuclear rim whereas LEDGF co-localization with H3K36me3 and BRD4 co-localization with H3K9/14ac occur further inside the nucleus.  相似文献   
65.
Social and economical development is closely associated with technological innovation and a well-developed biotechnological industry. In the last few years, Brazil’s scientific production has been steadily increasing; however, the number of patents is lagging behind, with technological and translational research requiring governmental incentive and reinforcement. The Cell and Molecular Therapy Center (NUCEL) was created to develop activities in the translational research field, addressing concrete problems found in biomedical and veterinary areas and actively searching for solutions by employing a genetic engineering approach to generate cell lines over-expressing recombinant proteins to be transferred to local biotech companies, aiming at furthering the development of a national competence for local production of biopharmaceuticals of widespread use and of life-saving importance. To this end, mammalian cell engineering technologies were used to generate cell lines over-expressing several different recombinant proteins of biomedical and biotechnological interest, namely, recombinant human Amylin/IAPP for diabetes treatment, human FVIII and FIX clotting factors for hemophilia, human and bovine FSH for fertility and reproduction, and human bone repair proteins (BMPs). Expression of some of these proteins is also being sought with the baculovirus/insect cell system (BEVS) which, in many cases, is able to deliver high-yield production of recombinant proteins with biological activity comparable to that of mammalian systems, but in a much more cost-effective manner. Transfer of some of these recombinant products to local Biotech companies has been pursued by taking advantage of the São Paulo State Foundation (FAPESP) and Federal Government (FINEP, CNPq) incentives for joint Research Development and Innovation partnership projects.  相似文献   
66.
The neural cell adhesion molecule (NCAM) plays a pivotal role in the development and maintenance of the nervous system via homophilic (NCAM–NCAM) and heterophilic (NCAM-other molecules) interactions. Many synthetic peptides have been engineered to mimic these interactions and induce NCAM-downstream signaling pathways. Such NCAM mimetics have displayed neuritogenic and neuroprotective properties, as well as synaptic modulation in vitro and in vivo. Furthermore, they have been used successfully in preclinical studies to treat neurological disorders including stroke, traumatic brain injury and Alzheimer’s disease. This review focuses on recent progress in the development of NCAM mimetic peptides, in particular, on establishing C3, plannexin, and FGL as therapeutic candidates for neurological disorders.  相似文献   
67.
68.
A full-length cDNA encoding a putative aspartic acid protease (AcAP1) was isolated for the first time from the flesh of pineapple (Ananas comosus) fruit. The deduced sequence of AcAP1 showed all the common features of a typical plant aspartic protease phytepsin precursor. Analysis of AcAP1 gene expression under postharvest chilling treatment in two pineapple varieties differing in their resistance to blackheart development revealed opposite trends. The resistant variety showed an up-regulation of AcAP1 precursor gene expression whereas the susceptible showed a down-regulation in response to postharvest chilling treatment. The same trend was observed regarding specific AP enzyme activity in both varieties. Taken together our results support the involvement of AcAP1 in postharvest chilling stress resistance in pineapple fruits.  相似文献   
69.
Summary Nikkomycin Z (NZ) is a competitive inhibitor of chitin synthase III in the yeast Saccharomyces cerevisiae. Myosin type II-deficient yeast strains (myo1) display a dramatic reduction in growth when chitin synthase III activity is inhibited by NZ, supporting the contention that actomyosin motility plays an important role in maintaining cell wall integrity. A proposed inhibitor of cortical actin polymerization in vitro, 2,3-butanedione monoxime (BDM), also inhibits growth of wild-type yeast strains at a concentration of 20 mM. In this study, we assayed for potential in vivo interplay between BDM-sensitive cell functions and cell wall chitin synthesis by testing for increased sensitivity to NZ during co-treatment with BDM at sub-inhibitory concentrations. Our results show that BDM can increase the sensitivity of yeast cells to Nikkomycin Z.  相似文献   
70.
Recognition that tree recruitment depends on the balance between seed arrival and seedling survival has led to a surge of interest in seed‐dispersal limitation and seedling‐establishment limitation in primary forests. Virtually unaddressed are comparisons of this balance in mature and early successional habitats. We assessed seed rain and seedling recruitment dynamics of tree species in primary forest, secondary forest and pasture released from grazing in a tropical agricultural landscape. Seed to seedling ratios (seed effectiveness; Φi) for 43 species in southern Mexico determined differences in the extent to which seeds produced seedlings by habitat, life history, and dispersal mode. Reproductive potential as estimated by the transition from seed rain to seedling recruitment, differed by habitats, and varied dramatically by life history and dispersal mode. Expected recruit densities (Eit) were higher for animal‐dispersed than wind‐dispersed species, and for non‐pioneer than pioneer species. Non‐pioneers and animal‐dispersed species had higher expected relative recruit abundance (εit) in primary forest (median of 4 seeds recruit?1) whereas in secondary forest wind‐dispersed pioneers had the highest expected relative recruit abundance (median of 16 seeds per recruit). In pastures, wind‐dispersed pioneer species were most successful with many more seeds per recruit (median of 291) than both forest habitats. Seeds per recruit (Φi) appeared to decrease with increase in seed mass for 43 species for which data were available (r = –0.55, P < 0.001). This was associated with a negative correlation of Φi with seed size in primary forest (r = –0.50, P = 0.08 for 13 species); Φi was not correlated with seed size in secondary forest (n = 16) or pasture (n = 14). Metrics of seeds per recruit, expected recruit density and expected relative recruit abundance dramatically illustrate differences in barriers to recruitment in successional habitats.  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