全文获取类型
收费全文 | 3629篇 |
免费 | 267篇 |
国内免费 | 5篇 |
出版年
2023年 | 22篇 |
2022年 | 45篇 |
2021年 | 58篇 |
2020年 | 52篇 |
2019年 | 52篇 |
2018年 | 62篇 |
2017年 | 54篇 |
2016年 | 93篇 |
2015年 | 168篇 |
2014年 | 204篇 |
2013年 | 269篇 |
2012年 | 283篇 |
2011年 | 262篇 |
2010年 | 189篇 |
2009年 | 152篇 |
2008年 | 239篇 |
2007年 | 232篇 |
2006年 | 177篇 |
2005年 | 183篇 |
2004年 | 201篇 |
2003年 | 185篇 |
2002年 | 133篇 |
2001年 | 43篇 |
2000年 | 16篇 |
1999年 | 36篇 |
1998年 | 42篇 |
1997年 | 28篇 |
1996年 | 31篇 |
1995年 | 29篇 |
1994年 | 29篇 |
1993年 | 18篇 |
1992年 | 23篇 |
1991年 | 22篇 |
1990年 | 22篇 |
1989年 | 27篇 |
1988年 | 19篇 |
1987年 | 21篇 |
1986年 | 15篇 |
1985年 | 13篇 |
1984年 | 18篇 |
1983年 | 11篇 |
1982年 | 10篇 |
1981年 | 9篇 |
1980年 | 13篇 |
1979年 | 7篇 |
1978年 | 10篇 |
1976年 | 9篇 |
1975年 | 9篇 |
1974年 | 11篇 |
1973年 | 6篇 |
排序方式: 共有3901条查询结果,搜索用时 70 毫秒
81.
82.
Dinara Azimova Nadia Herrera Lucian Duvenage Mark Voorhies Rosa A. Rodriguez Bevin C. English Jennifer C. Hoving Oren Rosenberg Anita Sil 《PLoS pathogens》2022,18(6)
Intracellular pathogens secrete effectors to manipulate their host cells. Histoplasma capsulatum (Hc) is a fungal intracellular pathogen of humans that grows in a yeast form in the host. Hc yeasts are phagocytosed by macrophages, where fungal intracellular replication precedes macrophage lysis. The most abundant virulence factor secreted by Hc yeast cells is Calcium Binding Protein 1 (Cbp1), which is absolutely required for macrophage lysis. Here we take an evolutionary, structural, and cell biological approach to understand Cbp1 function. We find that Cbp1 is present only in the genomes of closely related dimorphic fungal species of the Ajellomycetaceae family that lead primarily intracellular lifestyles in their mammalian hosts (Histoplasma, Paracoccidioides, and Emergomyces), but not conserved in the extracellular fungal pathogen Blastomyces dermatitidis. We observe a high rate of fixation of non-synonymous substitutions in the Cbp1 coding sequences, indicating that Cbp1 is under positive selection. We determine the de novo structures of Hc H88 Cbp1 and the Paracoccidioides americana (Pb03) Cbp1, revealing a novel “binocular” fold consisting of a helical dimer arrangement wherein two helices from each monomer contribute to a four-helix bundle. In contrast to Pb03 Cbp1, we show that Emergomyces Cbp1 orthologs are unable to stimulate macrophage lysis when expressed in the Hc cbp1 mutant. Consistent with this result, we find that wild-type Emergomyces africanus yeast are able to grow within primary macrophages but are incapable of lysing them. Finally, we use subcellular fractionation of infected macrophages and indirect immunofluorescence to show that Cbp1 localizes to the macrophage cytosol during Hc infection, making this the first instance of a phagosomal human fungal pathogen directing an effector into the cytosol of the host cell. We additionally show that Cbp1 forms a complex with Yps-3, another known Hc virulence factor that accesses the cytosol. Taken together, these data imply that Cbp1 is a fungal virulence factor under positive selection that localizes to the cytosol to trigger host cell lysis. 相似文献
83.
Limanjaya Anita Guo Nan Yin Soon-Sun Hong Ju-Hee Kang Yong Song Gho Jun-Kyu Suh Ji-Kan Ryu 《International journal of biological sciences》2022,18(9):3653
Diabetes mellitus is one of the main causes of erectile dysfunction (ED). Men with diabetic ED do not respond well to oral phosphodiesterase-5 inhibitors owing to neurovascular dysfunction. Pericyte-derived extracellular vesicle-mimetic nanovesicles (PC-NVs) are known to promote nerve regeneration in a mouse model of cavernous nerve injury. Here, we report that administration of PC-NVs effectively promoted penile angiogenesis and neural regeneration under diabetic conditions, thereby improving erectile function. Specifically, PC-NVs induced endothelial proliferation and migration and reduced cell apoptosis under diabetic conditions. In addition, PC-NVs induced neural regeneration in STZ-induced diabetic mice in dorsal root ganglion and major pelvic ganglion explants in vivo and ex vivo under high-glucose conditions. We found that lipocalin 2 (Lcn2) is a new target of PC-NVs in this process, demonstrating that PC-NVs exert their angiogenic and nerve-regeneration effects by activating MAP kinase and PI3K/Akt and suppressing P53 signaling pathway in an Lcn2-dependent manner. Our findings provide new conclusive evidence that PC-NVs can promote neurovascular regeneration and recovery of erectile function under diabetic conditions via an Lcn2-dependent mechanism. Thus, local administration of PC-NVs may be a promising treatment strategy for the treatment of diabetic ED. 相似文献
84.
85.
Structural and ecophysiological adaptations to forest gaps 总被引:2,自引:0,他引:2
Guilherme R. Rabelo Ângela P. Vitória Marcos V. A. da Silva Ricardo A. Cruz Elis I. B. Pinho Douglas R. Ribeiro Anita V. Freitas Maura Da Cunha 《Trees - Structure and Function》2013,27(1):259-272
To survive new microclimatic conditions of a forest gap environment, plant species must physiologically and structurally adjust. A morpho-anatomical, ultrastructural and ecophysiological study was performed at three different times in a forest gap that was created by illegal selective logging. The study followed the early successional Actinostemon verticillatus and the late-successional Metrodorea brevifolia, to elucidate the adaptive strategies of acclimation to gaps. Additionally, Schinus terebinthifolius was included in the study in order to test the plasticity of a pioneer species that grows on forest edges, where this species had higher values of leaf thickness, leaf mass area and succulence. M. brevifolia had succulent leaves, high leaf area and a thin cuticle. A. verticillatus presented the densest leaves and was the only species to show leaf morpho-anatomical plasticity. Ultrastructural and physiological differences were observed only in A. verticillatus and M. brevifolia leaves from the gap: increase in the stroma volume, oil droplets, plastoglobuli, photochemical and non-photochemical quenching. Photosynthetic efficiency showed that the early stages of gap formation are the most critical. Acclimation strategies of A. verticillatus suggest this species invests in the efficiency of photosynthesis by increasing its leaf thickness, leaf mass area and in water content maintenance by increasing the density of its leaves, at the expense of gas exchange, was compensated by a high density of stomata. M. brevifolia compensates for the higher cost of leaves and lower leaf plasticity with ultrastructural changes that are used to adjust the photosynthetic process, which promotes a shorter leaf payback time. 相似文献
86.
The association of interleukin-1β (IL-1B) -511C?>?T and IL-1 receptor antagonist (IL-1RN) VNTR, transforming growth factor-β (TGF-B1) +28C?>?T and interferon-γ (IFN-G)?+?874T>A polymorphisms with bladder cancer (CaB) susceptibility and risk of recurrence in Bacillus Calmette–Guérin (BCG)-treated patients was analyzed in 287 controls and 213 CaB patients (73 BCG treated). Increased risk was observed with the IL-1RN*2 allele (odds ratio (OR) 5.01) and the IFN-G +874 A allele (OR 1.78). TGF-B TT and IFN-G +874 A carriers were associated with reduced (hazard ratio (HR) 0.37) and enhanced (HR 2.24) risk of recurrence after BCG immunotherapy, respectively. The study suggests that cytokine gene variants may modulate CaB susceptibility and risk of recurrence after BCG immunotherapy. 相似文献
87.
Eric M. Lind Elizabeth Borer Eric Seabloom Peter Adler Jonathan D. Bakker Dana M. Blumenthal Mick Crawley Kendi Davies Jennifer Firn Daniel S. Gruner W. Stanley Harpole Yann Hautier Helmut Hillebrand Johannes Knops Brett Melbourne Brent Mortensen Anita C. Risch Martin Schuetz Carly Stevens Peter D. Wragg 《Ecology letters》2013,16(4):513-521
Plant growth can be limited by resource acquisition and defence against consumers, leading to contrasting trade‐off possibilities. The competition‐defence hypothesis posits a trade‐off between competitive ability and defence against enemies (e.g. herbivores and pathogens). The growth‐defence hypothesis suggests that strong competitors for nutrients are also defended against enemies, at a cost to growth rate. We tested these hypotheses using observations of 706 plant populations of over 500 species before and following identical fertilisation and fencing treatments at 39 grassland sites worldwide. Strong positive covariance in species responses to both treatments provided support for a growth‐defence trade‐off: populations that increased with the removal of nutrient limitation (poor competitors) also increased following removal of consumers. This result held globally across 4 years within plant life‐history groups and within the majority of individual sites. Thus, a growth‐defence trade‐off appears to be the norm, and mechanisms maintaining grassland biodiversity may operate within this constraint. 相似文献
88.
Neogenin has been implicated in a variety of developmental processes such as neurogenesis, neuronal differentiation, apoptosis, migration and axon guidance. Binding of repulsive guidance molecules (RGMs) to Neogenin inhibits axon outgrowth of different neuronal populations. This effect requires Neogenin to interact with co-receptors of the uncoordinated locomotion-5 (Unc5) family to activate downstream Rho signaling. Although previous studies have reported RGM, Neogenin, and/or Unc5 expression, a systematic comparison of RGM and Neogenin expression in the developing nervous system is lacking, especially at later developmental stages. Furthermore, information on RGM and Neogenin expression at the protein level is limited. To fill this void and to gain further insight into the role of RGM-Neogenin signaling during mouse neural development, we studied the expression of RGMa, RGMb, Neogenin and Unc5A-D using in situ hybridization, immunohistochemistry and RGMa section binding. Expression patterns in the primary olfactory system, cortex, hippocampus, habenula, and cerebellum were studied in more detail. Characteristic cell layer-specific expression patterns were detected for RGMa, RGMb, Neogenin and Unc5A-D. Furthermore, strong expression of RGMa, RGMb and Neogenin protein was found on several major axon tracts such as the primary olfactory projections, anterior commissure and fasciculus retroflexus. These data not only hint at a role for RGM-Neogenin signaling during the development of different neuronal systems, but also suggest that Neogenin partners with different Unc5 family members in different systems. Overall, the results presented here will serve as a framework for further dissection of the role of RGM-Neogenin signaling during neural development. 相似文献
89.
90.