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   5638篇
  免费   621篇
  国内免费   248篇
  2024年   27篇
  2023年   88篇
  2022年   130篇
  2021年   216篇
  2020年   332篇
  2019年   412篇
  2018年   282篇
  2017年   213篇
  2016年   227篇
  2015年   249篇
  2014年   286篇
  2013年   472篇
  2012年   250篇
  2011年   238篇
  2010年   223篇
  2009年   263篇
  2008年   285篇
  2007年   245篇
  2006年   235篇
  2005年   205篇
  2004年   188篇
  2003年   148篇
  2002年   158篇
  2001年   124篇
  2000年   90篇
  1999年   113篇
  1998年   93篇
  1997年   93篇
  1996年   53篇
  1995年   67篇
  1994年   56篇
  1993年   43篇
  1992年   49篇
  1991年   47篇
  1990年   40篇
  1989年   27篇
  1988年   28篇
  1987年   29篇
  1986年   23篇
  1985年   30篇
  1984年   20篇
  1983年   9篇
  1982年   24篇
  1981年   10篇
  1980年   12篇
  1979年   11篇
  1978年   8篇
  1977年   7篇
  1976年   9篇
  1974年   7篇
排序方式: 共有6507条查询结果,搜索用时 15 毫秒
71.
Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells and the use of potential chemotherapeutics in glioma by modulating MEG3 expression. Cell viability, migration and chemosensitivity were assayed. Cell death was evaluated in MEG3 overexpressing and MEG3 suppressed cells. MEG3 expression was compared in patient-derived glioma cells concerning IDH1 mutation and WHO grades. Silencing of MEG3 inhibited cell proliferation and reduced cell migration while overexpression of MEG3 promoted proliferation in glioma cells. MEG3 inhibition improved the chemosensitivity of glioma cells to 5-fluorouracil (5FU) but not to navitoclax. On the other hand, there is no significant effect of MEG3 expression on temozolamide (TMZ) treatment which is a standard chemotherapeutic agent in glioma. Suppression of the MEG3 gene in patient-derived oligodendroglioma cells also showed the same effect whereas glioblastoma cell proliferation and chemosensitivity were not affected by MEG3 inhibition. Further, as a possible cell death mechanism of action apoptosis was investigated. Although MEG3 is a widely known tumour suppressor gene and its loss is associated with several cancer types, here we reported that MEG3 inhibition can be used for improving the efficiency of known chemotherapeutic drug sensitivity. We propose that the level of MEG3 should be evaluated in the treatment of different glioma subtypes that are resistant to effective drugs to increase the potential effective drug applications.  相似文献   
72.
Birds use stopovers during migration to interrupt endurance flight in order to minimize immediate and/or future fitness costs. Stopovers on ships is considered an exceptional and anecdotal event in the ornithological literature. This does not match the experience we had in the summer of 2021, during an oceanographic campaign in the Central Mediterranean, when we regularly observed on average 2.8 birds, of at least 13 species, stopping on board during the 25 days of the campaign. The median stopping time was 42 min, ranging from a few minutes to overnight stays on board. The probability of finding a bird stopping aboard increased with wind force and cloud cover. Birds also stopped more often in a headwind and did not stop when the wind came from different directions other than the headwind. The Central Mediterranean is one of the busiest sea routes in the world, combining the mean daily number of birds on board with the thousands of ships that pass through it during the 3 months of summer migration; we estimate that nearly 4 million birds could use ships as stopover sites. This behaviour may represent a modern-day strategy that uses ships as stopovers in the event of adverse weather conditions or could act as an ecological trap, increasing the mortality of migrants. This phenomenon deserves more research attention and further studies recording body condition and tagging of individuals on board would be informative.  相似文献   
73.
Testes control the development of male reproductive system. The testicular interstitial Leydig cells (Leydig cells) synthesize testosterone for promoting spermatogenesis and secondary sexual characteristics. Type A platelet-derived growth factor (PDGF-AA) is one of the most important growth factors in regulating Leydig cell growth and function. Knockout of PDGF-AA or its congenital receptor PDGFR-α leads to poor testicular development caused by reducing Leydig cell numbers, supporting PDGF-AA/PDGFR-α signaling regulates Leydig cell development. Primary cilium is a cellular antenna that functions as an integrative platform to transduce extracellular signaling for proper development and differentiation. Several receptors including PDGFR-α are observed on primary cilia for initiating signaling cascades in distinct cell types. Here we showed that PDGF-AA/PDGFR-α signaling promoted Leydig cells growth, migration, and invasion via primary cilia. Upon PDGF-AA treatment, AKT and ERK signaling were activated to regulate these cellular events. Interestingly, active AKT and ERK were detected around the base of primary cilia. Depletion of ciliary genes (IFT88 and CEP164) alleviated PDGF-AA-activated AKT and ERK, thus reducing Leydig cell growth, migration, and invasion. Thus, our study not only reveals the function of PDGF-AA/PDGFR-α signaling in maintaining testicular physiology but also uncovers the role of primary cilium and downstream signaling in regulating Leydig cell development.  相似文献   
74.
分化聚类36(cluster of differentiation 36,CD36)是一种位于细胞表面的膜蛋白受体,可以结合并转运脂肪酸。内质网膜蛋白4B (Nogo-B)在肝脏中调控脂肪酸代谢而影响肝癌的发展。目前并不清楚CD36和Nogo-B的相互作用是否能够影响乳腺癌细胞的增殖和迁移。本研究在三阴性乳腺癌(triple-negative breast cancer,TNBC)细胞中同时干预CD36与Nogo-B的表达来探索它们对细胞增殖与迁移的影响。结果表明在三阴性乳腺癌细胞中,单独抑制CD36或Nogo-B的表达都能够抑制细胞的增殖与迁移;同时抑制CD36与Nogo-B的表达时,这种抑制效果更加明显,且Vimentin、B细胞淋巴瘤-2(B-cell lympoma-2,BCL2)和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达受到抑制。在小鼠移植瘤模型中,E0771细胞转染CD36或Nogo-B的siRNA后成瘤能力降低;同时敲减CD36和Nogo-B时,肿瘤生长速度显著减慢。机制研究发现,抑制CD36和Nogo-B表达能够抑制脂肪酸结合蛋白4(fatty acid binding protein 4,FABP4)和脂肪酸转运蛋白4(fatty acid transport protein 4,FATP4) mRNA的含量,同时CD36和Nogo-B过表达刺激的细胞增殖被FABP4的siRNA降低,预示着抑制乳腺癌细胞中CD36与Nogo-B的表达可能通过抑制脂肪酸的吸收和转运而抑制细胞的生长和迁移。此外,抑制CD36与Nogo-B的表达可激活P53-P21-Rb信号通路,参与抑制CD36与Nogo-B表达而抑制的细胞增殖与迁移。本研究证明同时抑制CD36和Nogo-B的表达能够协同抑制三阴性乳腺癌细胞的增殖和迁移,为临床抗三阴性乳腺癌药物的开发提供了新的靶点。  相似文献   
75.
目的 鼻咽癌是一种来源于鼻咽上皮的恶性肿瘤,其临床特征之一是易发生淋巴转移,但是目前鼻咽癌转移的分子机制尚未阐明。circPVT1是由PVT1基因2号外显子反向拼接形成的环状RNA (circRNA),在多种肿瘤中表达上调,本文探讨了circPVT1在鼻咽癌侵袭迁移中的作用和分子机制。方法 通过RT-qPCR检测circPVT1及其下游miRNA和FSCN1在鼻咽癌细胞的表达情况,Transwell和划痕愈合实验检测circPVT1对鼻咽癌细胞侵袭迁移的影响,RNA pull-down实验检测circPVT1结合的miRNA,双荧光素酶报告实验检测miR-24-3p和let-7a-5p靶向抑制FSCN1 mRNA表达。结果 在鼻咽癌细胞中过表达circPVT1可以促进鼻咽癌细胞侵袭迁移,而敲低circPVT1则可以抑制鼻咽癌细胞的侵袭迁移。进一步研究发现,circPVT1可以通过竞争性吸附miR-24-3p和let-7a-5p,上调FSCN1的表达,从而促进鼻咽癌细胞的侵袭迁移。结论 circPVT1通过miR-24-3p/let-7a-5p/FSCN1轴促进鼻咽癌细胞侵袭迁移,证实c...  相似文献   
76.
Endemic species are important components of regional biodiversity and hold the key to understanding local adaptation and evolutionary processes that shape species distributions. This study investigated the biogeographic history of a relict conifer Pinus bungeana Zucc. ex Endl. confined to central China. We examined genetic diversity in P. bungeana using genotyping-by-sequencing and chloroplast and mitochondrial DNA markers. We performed spatial and temporal inference of recent genetic and demographic changes, and dissected the impacts of geography and environmental gradients on population differentiation. We then projected P. bungeana's risk of decline under future climates. We found extremely low nucleotide diversity (average π 0.0014), and strong population structure (global FST 0.234) even at regional scales, reflecting long-term isolation in small populations. The species experienced severe bottlenecks in the early Pliocene and continued to decline in the Pleistocene in the western distribution, whereas the east expanded recently. Local adaptation played a small (8%) but significant role in population diversity. Low genetic diversity in fragmented populations makes the species highly vulnerable to climate change, particularly in marginal and relict populations. We suggest that conservation efforts should focus on enhancing gene pool and population growth through assisted migration within each genetic cluster to reduce the risk of further genetic drift and extinction.  相似文献   
77.
The aims of this study were to investigate the diet and relative abundance of fruit bats in a lowland Malaysian rain forest and to test the hypothesis that the local assemblage structure of fruit bats varies significantly over time in relation to the availability of food. In total, 352 fruit bats of eight species were captured during 72,306 m2 mist‐net hours of sampling between February 1996 and September 1999. Three species of fruit bats (Balionycteris maculita, Chironax melanocephalus, and Cynopterus brachyotis) that fed on a wide range of “steady state” and “big bang” food resources were captured continuously throughout the study period, with no significant variation in capture rates over time. In contrast, five species that fed exclusively or almost exclusively on “big bang” food resources were sampled intermittently, with significant temporal variation in the capture rates of two species (Cynopterus horsfieldi and Megaerops ecaudatus). Significant variation in the capture rates of the remaining three species (Dyacopterus spadiceus, Eonycteris spelaea, and Rousettus amplexicaudatus) could not be detected due to small sample sizes. Since ephemeral “big bang” food resources were only sporadically available within the study area and were associated with large canopy trees and strangler figs, these results suggest that food abundance, or the availability of specific food items, may be important factors limiting local fruit bat species diversity in old‐growth Paleotropical rain forest. Thus, only three fruit bat species were locally resident within the forest throughout the study period. Therefore, further studies on the ranging behavior and habitat requirements of Malaysian fruit bats are required to assess the adequacy of existing reserves and protected areas.  相似文献   
78.
Abstract The recent development of automatically operating, inexpensive vertical-looking radar (VLR) for entomological purposes has made it practical to carry out routine, automated monitoring of insect aerial migration throughout the year. In this paper we investigate whether such radars might have a role in monitoring and forecasting schemes designed to improve the management of the Brown Planthopper (BPH), Nilaparvata lugens , and of associated rice pest species in China. A survey of the literature revealed that these insects typically migrate at altitudes between 300 to 2 000 m above ground level, but calculations based on BPH radar scattering cross-sections indicated that the maximum altitude at which they individually produce signals analysable by current VLRs is only ˜ 240 m. We also show that coverage over most of the flight altitudes of BPH could be achieved by building a VLR using a wavelength of 8.8 mm instead of the 3.2 cm of existing VLR, but that such a radar would be expensive to build and to operate. We suggest that a more practical solution would be to use a 3.2 cm VLR as a monitor of the aerial movement of the larger species, from which the migration of rice pests in general might be inferred.  相似文献   
79.
Abstract: Six species of Nabidae (Heteroptera) were collected by standardized sweep net sampling in alfalfa fields in Thuringia, Germany, from 1993 to 1995: Nabis pseudoferus , N. ferus , N. brevis , N. major , Nabicula flavomarginata and Aptus mirmicoides . Colonization of a newly cultivated field was studied over a 3-year period. The density of all the studied nabid species was low (less than five individuals per 100 sweeps) and not related to time since colonization started, or to the distance from the margin of the field. Macropterous species were able to colonize the whole field within one season. The density of one macropterous species, N. pseudoferus , varied between the years of study and was mainly affected by the harvest regime. The brachypterous species reached the margin within one season but for density it took three seasons to reach satiated values also in the centre of the field. The abundance of the brachypterous N. brevis was significantly different both between years and sampling sites. This indicates the importance of the surroundings on the succession of this species. Nabis major , a fully winged species, showed a migration pattern intermediate to macropterous and brachypterous nabids. These results suggest that the total abundance of nabid predators cannot be predicted by time or distance from the expansion source (shelter belts). The abundance of brachypterous nabid individuals can be predicted from time since colonization but is best analysed at the species level.  相似文献   
80.
Summary Malignant features in three glioma cell lines were studied in four defined media of various complexity. The cell lines D37MG, D54MG, and GaMG were able to grow in monolayer culture in all media examined, and as multicellular tumor spheroids in the two most nutrient-rich media. In the defined media, none of the cell lines were able to migrate in a migration assay on poly-D-lysine-coated plastic surfaces. Flow cytometric analysis of the GaMG cell line demonstrated no medium-dependent selection of subclones of glioma cells in spheroids cultured for 30 d. Morphological diversity of spheroids varied according to the supplementation of the media. The capacity of glioma cells to invade cellular rat brain aggregates was intact in the media examined. However, glioma migration was severely inhibited by the lack of specific serum components. This study demonstrates that glioma growth and invasion was heterogenously preserved in the defined media used. Depending on the assay to be used in the study of glioma cell behavior, the degree of medium supplementation has to be considered.  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