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   2276篇
  免费   194篇
  2023年   7篇
  2022年   29篇
  2021年   41篇
  2020年   32篇
  2019年   35篇
  2018年   61篇
  2017年   36篇
  2016年   77篇
  2015年   134篇
  2014年   156篇
  2013年   158篇
  2012年   229篇
  2011年   219篇
  2010年   109篇
  2009年   119篇
  2008年   163篇
  2007年   155篇
  2006年   125篇
  2005年   132篇
  2004年   101篇
  2003年   94篇
  2002年   86篇
  2001年   15篇
  2000年   10篇
  1999年   16篇
  1998年   21篇
  1997年   21篇
  1996年   9篇
  1995年   11篇
  1994年   4篇
  1993年   2篇
  1992年   7篇
  1991年   5篇
  1990年   7篇
  1989年   4篇
  1988年   3篇
  1985年   3篇
  1984年   3篇
  1975年   1篇
  1974年   4篇
  1973年   1篇
  1972年   3篇
  1971年   4篇
  1970年   1篇
  1969年   2篇
  1968年   1篇
  1966年   2篇
  1959年   1篇
  1950年   1篇
  1929年   1篇
排序方式: 共有2470条查询结果,搜索用时 46 毫秒
71.
Sexual reproduction is a complex process that contributes to differences between the sexes and divergence between species. From a male’s perspective, sexual selection can optimize reproductive success by acting on the variance in mating success (pre-insemination selection) as well as the variance in fertilization success (post-insemination selection). The balance between pre- and post-insemination selection has not yet been investigated using a strong hypothesis-testing framework that directly quantifies the effects of post-insemination selection on the evolution of reproductive success. Here we use experimental evolution of a uniquely engineered genetic system that allows sperm production to be turned off and on in obligate male-female populations of Caenorhabditis elegans. We show that enhanced post-insemination competition increases the efficacy of selection and surpasses pre-insemination sexual selection in driving a polygenic response in male reproductive success. We find that after 10 selective events occurring over 30 generations post-insemination selection increased male reproductive success by an average of 5- to 7-fold. Contrary to expectation, enhanced pre-insemination competition hindered selection and slowed the rate of evolution. Furthermore, we found that post-insemination selection resulted in a strong polygenic response at the whole-genome level. Our results demonstrate that post-insemination sexual selection plays a critical role in the rapid optimization of male reproductive fitness. Therefore, explicit consideration should be given to post-insemination dynamics when considering the population effects of sexual selection.  相似文献   
72.
Colorectal cancer (CRC) is a high‐incidence malignancy worldwide which still needs better therapy options. Therefore, the aim of the present study was to investigate the responses of normal or malignant human intestinal epithelium to bone morphogenetic protein (BMP)‐9 and to find out whether the application of BMP‐9 to patients with CRC or the enhancement of its synthesis in the liver could be useful strategies for new therapy approaches. In silico analyses of CRC patient cohorts (TCGA database) revealed that high expression of the BMP‐target gene ID1, especially in combination with low expression of the BMP‐inhibitor noggin, is significantly associated with better patient survival. Organoid lines were generated from human biopsies of colon cancer (T‐Orgs) and corresponding non‐malignant areas (N‐Orgs) of three patients. The N‐Orgs represented tumours belonging to three different consensus molecular subtypes (CMS) of CRC. Overall, BMP‐9 stimulation of organoids promoted an enrichment of tumour‐suppressive gene expression signatures, whereas the stimulation with noggin had the opposite effects. Furthermore, treatment of organoids with BMP‐9 induced ID1 expression (independently of high noggin levels), while treatment with noggin reduced ID1.In summary, our data identify the ratio between ID1 and noggin as a new prognostic value for CRC patient outcome. We further show that by inducing ID1, BMP‐9 enhances this ratio, even in the presence of noggin. Thus, BMP‐9 is identified as a novel target for the development of improved anti‐cancer therapies of patients with CRC.  相似文献   
73.
74.
The diversity of fungal communities on three different historical monuments in the city of Vienna (Austria) was analyzed and compared to the fungal diversity of microfungi on rock in the original quarry located in a rural area (Zogelsdorf, Austria). The fungal strains isolated were characterized by morphology and the complete rock fungal community was identified based on molecular data, that is, by sequencing parts of the small ribosomal subunit (18S) and internal transcribed spacer region 1 (ITS1). The genera Coniothyrium, Epicoccum and Phoma were found to be dominant {on} monument and rock surfaces. Additionally, black yeasts such as Exophiala species and microcolonial fungi like Sarcinomyces and Coniosporium which hitherto were regarded as typical rock inhabitants in semi-arid environments are frequently found on all rock surfaces in Vienna. The biodiversity of the fungi in the urban environment was much higher than on the same rock type in a rural environment, this difference can be attributed to the elevated organic pollution in the city.  相似文献   
75.
Autosomal recessive spinal muscular atrophy with respiratory distress type 1 (SMARD1) is caused by mutations in the immunoglobulin -binding protein 2 (IGHMBP2) gene. Patients affected by the infantile form of SMARD1 present with early onset respiratory distress. So far, patients with neither juvenile onset nor with larger deletions/rearrangements in IGHMBP2 have been reported. In this study, we investigated one patient with infantile (4 months) and another with juvenile (4.3 years) onset of respiratory distress. Direct sequencing of all exons and flanking intron sequences in both patients revealed a mutation on only one allele. In both patients, we identified genomic rearrangements of the other allele of IGHMBP2 by means of Southern blotting. Putative breakpoints were confirmed by polymerase chain reaction on genomic and cDNA. The patient with juvenile onset had an Alu/Alu mediated rearrangement, which resulted in the loss of ~18.5 kb genomic DNA. At the mRNA level, this caused an in-frame deletion of exons 3–7. The patient with infantile onset had a complex rearrangement with two deletions and an inversion between intron 10 and 14. This rearrangement led to a frameshift at the mRNA level. Our results show that SMARD1 can be caused by genomic rearrangements at the IGHMBP2 gene locus. This may be missed by mere sequence analysis. Additionally, we demonstrate that juvenile onset SMARD1 may also be caused by mutations of IGHMBP2. The complex nature of the genomic rearrangement in the patient with infantile SMARD1 is discussed and a deletion mechanism is proposed.  相似文献   
76.
RNAs that localize to the vegetal cortex of Xenopus oocytes are involved in early embryonic patterning and cell fate specification. Two mechanistically distinct pathways lead to RNA enrichment at the vegetal cortex: the early and the late. While several candidate proteins that seem to operate in the late localization pathway have been identified, proteins involved in the early pathway remain to be identified. In this study, we report on the isolation of a novel vegetally localized RNA in Xenopus oocytes that makes use of the early pathway and encodes a protein with a conserved but functionally uncharacterized NIF-motif. The localization signal of XNIF was mapped to a 300-nucleotide region in the 5'-UTR, which is able to mediate both accumulation to the mitochondrial cloud in stage I oocytes, as well as vegetal transport in later stage oocytes. The XNIF-LE contains 16 copies of the previously defined CAC-containing signal motifs for RNA localization. A critical number of such repeats seems to be required for accumulation in the mitochondrial cloud along the early pathway, but additional repeats seem to be required for localization along the late pathway. Cross-linking experiments identify two novel proteins of 62 and 64 kDa that interact with the XNIF-LE but not with the Vg1-LE that operates in the late pathway. Conversely, at least two of the previously identified VgRBPs, Vg1RBP1 and Prrp, also bind to the XNIF-LE. Thus, overlapping, but not identical, protein machineries mediate vegetal RNA localization along early and late pathways in Xenopus oocytes.  相似文献   
77.
The current study represents the first systematic investigation of the social communication of captive siamangs (Symphalangus syndactylus). The focus was on intentional signals, including tactile and visual gestures, as well as facial expressions and actions. Fourteen individuals from different groups were observed and the signals used by individuals were recorded. Thirty-one different signals, consisting of 12 tactile gestures, 8 visual gestures, 7 actions, and 4 facial expressions, were observed, with tactile gestures and facial expressions appearing most frequently. The range of the signal repertoire increased steadily until the age of six, but declined afterwards in adults. The proportions of the different signal categories used within communicative interactions, in particular actions and facial expressions, also varied depending on age. Group differences could be traced back mainly to social factors or housing conditions. Differences in the repertoire of males and females were most obvious in the sexual context. Overall, most signals were used flexibly, with the majority performed in three or more social contexts and almost one-third of signals used in combination with other signals. Siamangs also adjusted their signals appropriately for the recipient, for example, using visual signals most often when the recipient was already attending (audience effects). These observations are discussed in the context of siamang ecology, social structure, and cognition.To see video sequences of signals described here, please go to  相似文献   
78.
The so-called carousel setup has been widely utilized for testing the hypotheses of adverse health effects on the central nervous system (CNS) due to mobile phone exposures in the frequency bands 800-900 MHz. The objectives of this article were to analyze the suitability of the setup for the upper mobile frequency range, i.e., 1.4-2 GHz, and to conduct a detailed experimental and numerical dosimetry for the setup at the IRIDIUM frequency band of 1.62 GHz. The setup consists of a plastic base on which ten rats, restrained in radially positioned tubes, are exposed to the electromagnetic field emanating from a sleeved dipole antenna at the center. Latest generation miniaturized dosimetric E field and temperature probes were used to measure the specific absorption rate (SAR) inside the brain of three rat cadavers of the Lewis strain and two rat cadavers of the Fisher 344 strain. A numerical analysis was conducted on the basis of three numerical rat phantoms with voxel sizes between 1.5 and 0.125 mm3 that are based on high resolution MRI scans of a 300 g male Wistar rat and a 370 g male Sprague-Dawley rat. The average of the assessed SAR values in the brain was 2.8 mW/g per W antenna input power for adult rats with masses between 220 and 350 g and 5.3 mW/g per W antenna input power for a juvenile rat with a mass of 95 g. The strong increase of the SAR in the brain with decreasing animal size was verified by simulations of the absorption in numerical phantoms scaled to sizes between 100 and 500 g with three different scaling methods. The study also demonstrated that current rat phantom models do not provide sufficient spatial resolution to perform absolute SAR assessment for the brain tissue. The variation of the SAR(brain)(av) due to changes in position was assessed to be in the range from +15% to -30%. A study on the dependence of the performance of the carousel setup on the frequency revealed that efficiency, defined as SAR(brain)(av) per W antenna input power, and the ratio between SAR(brain)(av) and SAR(body)(av) are optimal in the mobile communications frequency range, i.e., 0.8-3 GHz.  相似文献   
79.
In most animal phyla from insects to mammals, there is a clear division of somatic and germ line cells. This is however not the case in plants and some animal phyla including tunicates, flatworms and the basal phylum Cnidaria, where germ stem cells arise de novo from somatic cells. Piwi-like genes represent essential stem cell genes in diverse multicellular organisms. The cnidarian Piwihomolog Cniwiwas cloned from Podocoryne carnea, a hydrozoan with a full life cycle. CniwiRNA is present in all developmental stages with highest levels in the egg and the medusa. In the adult medusa, Cniwi expression is prominent in the gonads where it likely functions as a germ stem cell gene. The gene is also expressed, albeit at low levels, in differentiated somatic cells like the striated muscle of the medusa. Isolated striated muscle cells can be induced to transdifferentiate into smooth muscle cells which proliferate and differentiate into nerve cells. Cniwi expression is upregulated transiently after induction of transdifferentiation and again when the emerging smooth muscle cells proliferate and differentiate. The continuous low-level expression of an inducible stem cell gene in differentiated somatic cells may underlie the ability to form medusa buds from polyp cells and explain the extraordinary transdifferentation and regeneration potential of Podocoryne carnea.  相似文献   
80.
The aim of a large number of studies on G protein-coupled receptors was centered on understanding the structural basis of their main functional properties. Here, we will briefly review the results obtained on the alpha1-adrenergic receptor subtypes belonging to the rhodopsin-like family of receptors. These findings contribute, on the one hand, to further understand the molecular basis of adrenergic transmission and, on the other, to provide some generalities on the structure-functional relationship of G protein-coupled receptors.  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