全文获取类型
收费全文 | 2370篇 |
免费 | 162篇 |
国内免费 | 1篇 |
专业分类
2533篇 |
出版年
2023年 | 6篇 |
2022年 | 38篇 |
2021年 | 63篇 |
2020年 | 32篇 |
2019年 | 40篇 |
2018年 | 52篇 |
2017年 | 38篇 |
2016年 | 63篇 |
2015年 | 113篇 |
2014年 | 109篇 |
2013年 | 149篇 |
2012年 | 180篇 |
2011年 | 183篇 |
2010年 | 137篇 |
2009年 | 113篇 |
2008年 | 173篇 |
2007年 | 149篇 |
2006年 | 148篇 |
2005年 | 153篇 |
2004年 | 107篇 |
2003年 | 119篇 |
2002年 | 100篇 |
2001年 | 19篇 |
2000年 | 22篇 |
1999年 | 24篇 |
1998年 | 32篇 |
1997年 | 15篇 |
1996年 | 17篇 |
1995年 | 9篇 |
1994年 | 14篇 |
1993年 | 11篇 |
1992年 | 12篇 |
1991年 | 3篇 |
1990年 | 13篇 |
1989年 | 4篇 |
1988年 | 9篇 |
1987年 | 9篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 9篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1978年 | 4篇 |
1976年 | 2篇 |
1974年 | 7篇 |
1969年 | 1篇 |
1963年 | 1篇 |
1897年 | 1篇 |
排序方式: 共有2533条查询结果,搜索用时 15 毫秒
41.
Ammar Jabali Anne Hoffrichter Ana Uzquiano Fabio Marsoner Ruven Wilkens Marco Siekmann Bettina Bohl Andrea C Rossetti Sandra Horschitz Philipp Koch Fiona Francis Julia Ladewig 《EMBO reports》2022,23(5)
Malformations of human cortical development (MCD) can cause severe disabilities. The lack of human‐specific models hampers our understanding of the molecular underpinnings of the intricate processes leading to MCD. Here, we use cerebral organoids derived from patients and genome edited‐induced pluripotent stem cells to address pathophysiological changes associated with a complex MCD caused by mutations in the echinoderm microtubule‐associated protein‐like 1 (EML1) gene. EML1‐deficient organoids display ectopic neural rosettes at the basal side of the ventricular zone areas and clusters of heterotopic neurons. Single‐cell RNA sequencing shows an upregulation of basal radial glial (RG) markers and human‐specific extracellular matrix components in the ectopic cell population. Gene ontology and molecular analyses suggest that ectopic progenitor cells originate from perturbed apical RG cell behavior and yes‐associated protein 1 (YAP1)‐triggered expansion. Our data highlight a progenitor origin of EML1 mutation‐induced MCD and provide new mechanistic insight into the human disease pathology. 相似文献
42.
43.
The molecule serotonin (5-hydroxytryptamine or 5-HT) is involved in numerous biological processes both inside and outside of the central nervous system. 5-HT signals through 5-HT receptors and it is the diversity of these receptors and their subtypes that give rise to the varied physiological responses. It is clear that platelet derived serotonin is critical for normal wound healing in multiple organs including, liver, lung heart and skin. 5-HT stimulates both vasoconstriction and vasodilation, influences inflammatory responses and promotes formation of a temporary scar which acts as a scaffold for normal tissue to be restored. However, in situations of chronic injury or damage 5-HT signaling can have deleterious effects and promote aberrant wound healing resulting in tissue fibrosis and impaired organ regeneration. This review highlights the diverse actions of serotonin signaling in the pathogenesis of fibrotic disease and explores how modulating the activity of specific 5-HT receptors, in particular the 5-HT2 subclass could have the potential to limit fibrosis and restore tissue regeneration. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. 相似文献
44.
Christian P Craddock Nicolette Adams Fiona M Bryant Smita Kurup Peter J Eastmond 《Plant signaling & behavior》2015,10(10)
Coordination of membrane lipid biosynthesis is important for cell function during plant growth and development. Here we summarize our recent work on PHOSPHATIDIC ACID PHOSPHOHYDROLASE (PAH) which suggests that this enzyme is a key regulator of phosphaticylcholine (PC) biosynthesis in Arabidopsis thaliana. Disruption of PAH activity elevates phosphatidic acid (PA) levels and stimulates PC biosynthesis and biogenesis of the endoplasmic reticulum (ER). Furthermore, the activity of PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE (CCT), which is the key enzyme controlling the rate of PC biosynthesis, is directly stimulated by PA and expression of a constitutively active version of CCT replicates the effects of PAH disruption. Hence PAH activity can control the abundance of PA, which in turn can modulate CCT activity to govern the rate of PC biosynthesis. Crucially it is not yet clear how PAH activity is regulated in Arabidopsis but there is evidence that PAH1 and PAH2 are both phosphorylated and further work will be required to investigate whether this is functionally significant. 相似文献
45.
46.
Marcello De Vitis Fiona R. Hay John B. Dickie Clare Trivedi Jaeyong Choi Rob Fiegener 《Restoration Ecology》2020,28(Z3):S249-S255
Effective seed storage after sourcing (harvesting or purchasing) is critical to restoration practitioners and native seed producers, as it is key to maintaining seed viability. Inadequate seed storage can lead to a waste of both natural and economic resources when seeds of poor quality are sown. When working with native species with unknown storage behavior, general assumptions can be made based on studies on related species, and standard practices may be applied with caution; however, an investigation should be conducted to understand if specific storage requirements are needed and for how long seeds can be stored before they lose significant viability. In this paper of the Special Issue Standards for Native Seeds in Ecological Restoration, we provide an overview of the key concepts in seed storage and the steps to take for effective storage of native seeds for restoration use. 相似文献
47.
Klara M. Wanelik Joanne S. Griffin Megan L. Head Fiona C. Ingleby Zenobia Lewis 《Ecology and evolution》2020,10(14):6870-6880
The academic disciplines of Science, Technology, Engineering and Mathematics (STEM) have long suffered from a lack of diversity. While in recent years there has been some progress in addressing the underrepresentation of women in STEM subjects, other characteristics that have the potential to impact on equality of opportunity have received less attention. In this study, we surveyed 188 early career scientists (ECRs), defined as within 10 years of completing their PhD, in the fields of ecology, evolutionary biology, behaviour, and related disciplines. We examined associations between ethnicity, age, sexual orientation, sex, socioeconomic background, and disability, with measures of career progression, namely publication record, number of applications made before obtaining a postdoc, type of contract, and number of grant applications made. We also queried respondents on perceived barriers to progression and potential ways of overcoming them. Our key finding was that socioeconomic background and ethnicity were associated with measures of career progression. While there was no difference in the number of reported first‐authored papers on PhD completion, ethnic minority respondents reported fewer other‐authored papers. In addition, ECRs from a lower socioeconomic background were more likely to report being in teaching and research positions, rather than research‐only positions, the latter being perceived as more prestigious by some institutions. We discuss our findings in the context of possible inequality of opportunity. We hope that this study will stimulate wider discussion and help to inform strategies to address the underrepresentation of minority groups in the fields of ecology and evolution, and STEM subjects more widely. 相似文献
48.
Damer P. Blake Vladimir Vrba Dong Xia Isa Danladi Jatau Simon Spiro Matthew J. Nolan Greg Underwood Fiona M. Tomley 《International journal for parasitology》2021,51(8):621-634
More than 68 billion chickens were produced globally in 2018, emphasising their major contribution to the production of protein for human consumption and the importance of their pathogens. Protozoan Eimeria spp. are the most economically significant parasites of chickens, incurring global costs of more than UK £10.4 billion per annum. Seven Eimeria spp. have long been recognised to infect chickens, with three additional cryptic operational taxonomic units (OTUs) first described more than 10 years ago. As the world’s farmers attempt to reduce reliance on routine use of antimicrobials in livestock production, replacing drugs that target a wide range of microbes with precise species- and sometimes strain-specific vaccines, the breakthrough of cryptic genetic types can pose serious problems. Consideration of biological characteristics including oocyst morphology, pathology caused during infection and pre-patent periods, combined with gene-coding sequences predicted from draft genome sequence assemblies, suggest that all three of these cryptic Eimeria OTUs possess sufficient genetic and biological diversity to be considered as new and distinct species. The ability of these OTUs to compromise chicken bodyweight gain and escape immunity induced by current commercially available anticoccidial vaccines indicates that they could pose a notable threat to chicken health, welfare, and productivity. We suggest the names Eimeria lata n. sp., Eimeria nagambie n. sp. and Eimeria zaria n. sp. for OTUs x, y and z, respectively, reflecting their appearance (x) or the origins of the first isolates of these novel species (y, z). 相似文献
49.
Whitfield Alan K. Adams Janine B. Harrison Trevor D. Lamberth Stephen J. Lemley Daniel A. MacKay Fiona Van Niekerk Lara Weyl Olaf L. F. 《Biological invasions》2021,23(9):2729-2747
Biological Invasions - We review the possible impacts of non-native biota on the indigenous fishes of South African estuaries, including macrophytes, algae, pathogens, invertebrates, and fishes.... 相似文献
50.
Maria Davern Noel E. Donlon Andrew Sheppard Fiona O’ Connell Conall Hayes Anshul Bhardwaj Emma Foley Dermot O’ Toole Niamh Lynam-Lennon Narayanasamy Ravi John V. Reynolds Stephen G. Maher Joanne Lysaght 《Translational oncology》2021,14(6):101062
Use of immune checkpoint inhibitors (ICIs) with chemotherapy to enhance responses in oesophageal adenocarcinoma (OAC) is an attractive approach. We identified subpopulations of OAC cells expressing inhibitory immune checkpoint (IC) ligands (PD-L1, PD-L2 and CD160) and receptors (PD-1, TIGIT, TIM-3, LAG-3 and A2aR) in vitro and in ex vivo biopsies. Combination chemotherapy regimens FLOT and CROSS promote a more immune-resistant phenotype through upregulation of IC ligands and receptors on OAC cells in vitro. Importantly, this study investigated if OAC cells, enriched for ICs exhibited a more stem-like and senescent-like phentoype. FLOT preferentially upregulates PD-L1 on a stem-like OAC cell phenotype, defined by ALDH activity. Expression of senescence-associated β-galactosidase is induced in a subpopulation of OAC cells following FLOT and CROSS chemotherapy treatment, along with enhanced expression of TIM-3 and A2aR ICs. Blockade of PD-1 signalling in OAC cells induced apoptosis and enhanced FLOT and CROSS chemotherapy toxicity in vitro. Upregulation of ICs on OAC cells following chemotherapy may represent potential mechanisms of chemo-immune resistance. Combination ICIs may be required to enhance the efficacy of chemotherapy and immunotherapy in OAC patients. 相似文献