全文获取类型
收费全文 | 3576篇 |
免费 | 367篇 |
出版年
2022年 | 28篇 |
2021年 | 52篇 |
2020年 | 35篇 |
2019年 | 31篇 |
2018年 | 58篇 |
2017年 | 41篇 |
2016年 | 104篇 |
2015年 | 171篇 |
2014年 | 188篇 |
2013年 | 204篇 |
2012年 | 268篇 |
2011年 | 262篇 |
2010年 | 186篇 |
2009年 | 118篇 |
2008年 | 203篇 |
2007年 | 204篇 |
2006年 | 207篇 |
2005年 | 178篇 |
2004年 | 152篇 |
2003年 | 150篇 |
2002年 | 116篇 |
2001年 | 72篇 |
2000年 | 89篇 |
1999年 | 67篇 |
1998年 | 30篇 |
1997年 | 24篇 |
1996年 | 27篇 |
1995年 | 18篇 |
1994年 | 20篇 |
1993年 | 27篇 |
1992年 | 36篇 |
1991年 | 36篇 |
1990年 | 38篇 |
1989年 | 27篇 |
1988年 | 28篇 |
1987年 | 23篇 |
1986年 | 21篇 |
1985年 | 21篇 |
1984年 | 25篇 |
1983年 | 25篇 |
1982年 | 19篇 |
1981年 | 20篇 |
1979年 | 20篇 |
1978年 | 15篇 |
1977年 | 21篇 |
1974年 | 17篇 |
1973年 | 21篇 |
1972年 | 16篇 |
1969年 | 21篇 |
1967年 | 12篇 |
排序方式: 共有3943条查询结果,搜索用时 15 毫秒
81.
82.
G. Stoelken K. Pritsch J. Simon C. W. Mueller T. E. E. Grams J. Esperschuetz 《Plant biosystems》2013,147(3):537-546
Abstract In a lysimeter study with young beech trees, the effects of elevated ozone concentration on the decomposition and fate of nitrogen in 15N‐labeled leaf litter were analyzed after one growing season. Nitrogen in the litter was dominated by a relatively inert, residual fraction, but easily decomposable nitrogen was present in substantial amounts. Nitrogen loss was significantly higher at twice‐ambient ozone which was largely attributed to an enhanced mobilization of residual nitrogen. Enhanced mobilization of nitrogen from litter at twice‐ambient ozone exposure resulted in additional 15N incorporation into the soil down to 30 cm depth. Only 0.41–0.62% of the nitrogen in the litter was incorporated into plant material at both ozone concentrations. Twice‐ambient ozone exposure changed the distribution of the nitrogen taken up from litter inside the beech trees in favor of the shoot, where it may have been used in biosynthetic processes required for defense reactions. 相似文献
83.
84.
Ivo Geikie Cobb 《BMJ (Clinical research ed.)》1914,1(2790):1349-1350
85.
Richard W. Clayton Ewan A. Langan David M. Ansell Ivo J. H. M. de Vos Klaus Gbel Marlon R. Schneider Mauro Picardo Xinhong Lim Maurice A. M. van Steensel Ralf Paus 《Biological reviews of the Cambridge Philosophical Society》2020,95(3):592-624
The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro‐regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α‐melanocyte‐stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro‐autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin‐mediated or facial paresis‐associated reduction of human sebum secretion suggests that cutaneous nerve‐derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin. 相似文献
86.
Olivo Miotto Makoto Sekihara Shin-Ichiro Tachibana Masato Yamauchi Richard D. Pearson Roberto Amato Sonia Gonalves Somya Mehra Rintis Noviyanti Jutta Marfurt Sarah Auburn Ric N. Price Ivo Mueller Mie Ikeda Toshiyuki Mori Makoto Hirai Livingstone Tavul Manuel W. Hetzel Moses Laman Alyssa E. Barry Pascal Ringwald Jun Ohashi Francis Hombhanje Dominic P. Kwiatkowski Toshihiro Mita 《PLoS pathogens》2020,16(12)
The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants’ genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites’ drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance. 相似文献
87.
Marie Spohn Karolin Müller Carmen Hschen Carsten W. Mueller Sven Marhan 《Global Change Biology》2020,26(3):1926-1935
Dark, that is, nonphototrophic, microbial CO2 fixation occurs in a large range of soils. However, it is still not known whether dark microbial CO2 fixation substantially contributes to the C balance of soils and what factors control this process. Therefore, the objective of this study was to quantitate dark microbial CO2 fixation in temperate forest soils, to determine the relationship between the soil CO2 concentration and dark microbial CO2 fixation, and to estimate the relative contribution of different microbial groups to dark CO2 fixation. For this purpose, we conducted a 13C‐CO2 labeling experiment. We found that the rates of dark microbial CO2 fixation were positively correlated with the CO2 concentration in all soils. Dark microbial CO2 fixation amounted to up to 320 µg C kg?1 soil day?1 in the Ah horizon. The fixation rates were 2.8–8.9 times higher in the Ah horizon than in the Bw1 horizon. Although the rates of dark microbial fixation were small compared to the respiration rate (1.2%–3.9% of the respiration rate), our findings suggest that organic matter formed by microorganisms from CO2 contributes to the soil organic matter pool, especially given that microbial detritus is more stable in soil than plant detritus. Phospholipid fatty acid analyses indicated that CO2 was mostly fixed by gram‐positive bacteria, and not by fungi. In conclusion, our study shows that the dark microbial CO2 fixation rate in temperate forest soils increases in periods of high CO2 concentrations, that dark microbial CO2 fixation is mostly accomplished by gram‐positive bacteria, and that dark microbial CO2 fixation contributes to the formation of soil organic matter. 相似文献
88.
Emma Colucci-Guyon Aline Rifflet Sarah Saint-Auret Anaëlle da Costa Laurent Boucontet Thomas Laval Christophe Prehaud Nicolas Blanchard Jean-Pierre Levraud Ivo G. Boneca Caroline Demangel Laure Guenin-Mac 《PLoS neglected tropical diseases》2020,14(12)
Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU) disease, is unique amongst human pathogens in its capacity to produce a lipid toxin called mycolactone. While previous studies have demonstrated that bacterially-released mycolactone diffuses beyond infection foci, the spatiotemporal distribution of mycolactone remained largely unknown. Here, we used the zebrafish model to provide the first global kinetic analysis of mycolactone’s diffusion in vivo, and multicellular co-culture systems to address the critical question of the toxin’s access to the brain.Zebrafish larvae were injected with a fluorescent-derivative of mycolactone to visualize the in vivo diffusion of the toxin from the peripheral circulation. A rapid, body-wide distribution of mycolactone was observed, with selective accumulation in tissues near the injection site and brain, together with an important excretion through the gastro-intestinal tract. Our conclusion that mycolactone reached the central nervous system was reinforced by an in cellulo model of human blood brain barrier and a mouse model of M. ulcerans-infection.Here we show that mycolactone has a broad but heterogenous profile of distribution in vivo. Our investigations in vitro and in vivo support the view that a fraction of bacterially-produced mycolactone gains access to the central nervous system. The relative persistence of mycolactone in the bloodstream suggests that assays of circulating mycolactone are relevant for BU disease monitoring and treatment optimization. 相似文献
89.
Victoria M. Stevens Scott W. Mueller Paul M. Reynolds Robert MacLaren Tyree H. Kiser 《Current fungal infection reports》2020,14(1):50-62
This article aimed to review animal models of antifungals and identifies human literature to assess if the extrapolation of results is reliable. Animal studies have helped identify area under the concentration curve to minimum inhibitory concentration ratio targets for new drugs and formulations such as isavuconazole and delayed-release posaconazole that have translated to successful outcomes in humans. Models have also been influential in the identification of possible combination therapies for the treatment of aspergillosis, such as voriconazole and echinocandins. However, challenges are endured with animal models when it comes to replicating the pharmacokinetics of humans which has been exemplified with the newest itraconazole formulation. Additionally, animal models have displayed a survival benefit with the use of iron chelators and amphotericin for mucormycosis which was not demonstrated in humans. Animal models have been a staple in the development and optimization of antifungal agents. They afford the ability to investigate uncommon diseases, such as invasive fungal infections, that would otherwise take years and many resources to complete. Although there are many benefits of animal models, there are also shortcomings. This is why the reliability of extrapolating data from animal models to humans is often scrutinized. 相似文献
90.
Noe Fernandez‐Pozo Fabian B. Haas Rabea Meyberg Kristian K. Ullrich Manuel Hiss Pierre‐Franois Perroud Sebastian Hanke Viktor Kratz Adrian F. Powell Eleanor F. Vesty Christopher G. Daum Matthew Zane Anna Lipzen Avinash Sreedasyam Jane Grimwood Juliet C. Coates Kerrie Barry Jeremy Schmutz Lukas A. Mueller Stefan A. Rensing 《The Plant journal : for cell and molecular biology》2020,102(1):165-177
Physcomitrella patens is a bryophyte model plant that is often used to study plant evolution and development. Its resources are of great importance for comparative genomics and evo‐devo approaches. However, expression data from Physcomitrella patens were so far generated using different gene annotation versions and three different platforms: CombiMatrix and NimbleGen expression microarrays and RNA sequencing. The currently available P. patens expression data are distributed across three tools with different visualization methods to access the data. Here, we introduce an interactive expression atlas, Physcomitrella Expression Atlas Tool (PEATmoss), that unifies publicly available expression data for P. patens and provides multiple visualization methods to query the data in a single web‐based tool. Moreover, PEATmoss includes 35 expression experiments not previously available in any other expression atlas. To facilitate gene expression queries across different gene annotation versions, and to access P. patens annotations and related resources, a lookup database and web tool linked to PEATmoss was implemented. PEATmoss can be accessed at https://peatmoss.online.uni-marburg.de 相似文献