全文获取类型
收费全文 | 8856篇 |
免费 | 670篇 |
国内免费 | 670篇 |
专业分类
10196篇 |
出版年
2024年 | 19篇 |
2023年 | 114篇 |
2022年 | 282篇 |
2021年 | 492篇 |
2020年 | 295篇 |
2019年 | 373篇 |
2018年 | 378篇 |
2017年 | 302篇 |
2016年 | 366篇 |
2015年 | 567篇 |
2014年 | 691篇 |
2013年 | 705篇 |
2012年 | 829篇 |
2011年 | 721篇 |
2010年 | 434篇 |
2009年 | 407篇 |
2008年 | 463篇 |
2007年 | 382篇 |
2006年 | 294篇 |
2005年 | 246篇 |
2004年 | 191篇 |
2003年 | 184篇 |
2002年 | 162篇 |
2001年 | 143篇 |
2000年 | 128篇 |
1999年 | 106篇 |
1998年 | 71篇 |
1997年 | 83篇 |
1996年 | 82篇 |
1995年 | 59篇 |
1994年 | 47篇 |
1993年 | 45篇 |
1992年 | 63篇 |
1991年 | 49篇 |
1990年 | 49篇 |
1989年 | 33篇 |
1988年 | 39篇 |
1987年 | 26篇 |
1986年 | 23篇 |
1985年 | 36篇 |
1984年 | 33篇 |
1983年 | 14篇 |
1982年 | 15篇 |
1981年 | 8篇 |
1978年 | 11篇 |
1974年 | 11篇 |
1973年 | 7篇 |
1971年 | 9篇 |
1967年 | 7篇 |
1966年 | 9篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
231.
Jennifer D. Watts Mary Farina John S. Kimball Luke D. Schiferl Zhihua Liu Kyle A. Arndt Donatella Zona Ashley Ballantyne Eugénie S. Euskirchen Frans-Jan W. Parmentier Manuel Helbig Oliver Sonnentag Torbern Tagesson Janne Rinne Hiroki Ikawa Masahito Ueyama Hideki Kobayashi Torsten Sachs Daniel F. Nadeau John Kochendorfer Marcin Jackowicz-Korczynski Anna Virkkala Mika Aurela Roisin Commane Brendan Byrne Leah Birch Matthew S. Johnson Nima Madani Brendan Rogers Jinyang Du Arthur Endsley Kathleen Savage Ben Poulter Zhen Zhang Lori M. Bruhwiler Charles E. Miller Scott Goetz Walter C. Oechel 《Global Change Biology》2023,29(7):1870-1889
Arctic-boreal landscapes are experiencing profound warming, along with changes in ecosystem moisture status and disturbance from fire. This region is of global importance in terms of carbon feedbacks to climate, yet the sign (sink or source) and magnitude of the Arctic-boreal carbon budget within recent years remains highly uncertain. Here, we provide new estimates of recent (2003–2015) vegetation gross primary productivity (GPP), ecosystem respiration (Reco), net ecosystem CO2 exchange (NEE; Reco − GPP), and terrestrial methane (CH4) emissions for the Arctic-boreal zone using a satellite data-driven process-model for northern ecosystems (TCFM-Arctic), calibrated and evaluated using measurements from >60 tower eddy covariance (EC) sites. We used TCFM-Arctic to obtain daily 1-km2 flux estimates and annual carbon budgets for the pan-Arctic-boreal region. Across the domain, the model indicated an overall average NEE sink of −850 Tg CO2-C year−1. Eurasian boreal zones, especially those in Siberia, contributed to a majority of the net sink. In contrast, the tundra biome was relatively carbon neutral (ranging from small sink to source). Regional CH4 emissions from tundra and boreal wetlands (not accounting for aquatic CH4) were estimated at 35 Tg CH4-C year−1. Accounting for additional emissions from open water aquatic bodies and from fire, using available estimates from the literature, reduced the total regional NEE sink by 21% and shifted many far northern tundra landscapes, and some boreal forests, to a net carbon source. This assessment, based on in situ observations and models, improves our understanding of the high-latitude carbon status and also indicates a continued need for integrated site-to-regional assessments to monitor the vulnerability of these ecosystems to climate change. 相似文献
232.
233.
234.
Hao Chen Peng Tan Baolin Qian Yichao Du Ankang Wang Hao Shi Zhiwei Huang Shiyao Huang Tiancheng Liang Wenguang Fu 《Journal of cellular and molecular medicine》2020,24(2):1488-1503
Chronic pancreatitis (CP), characterized by pancreatic fibrosis, is a recurrent, progressive and irreversible disease. Activation of the pancreatic stellate cells (PSCs) is considered a core event in pancreatic fibrosis. In this study, we investigated the role of hydrogen peroxide‐inducible clone‐5 (Hic‐5) in CP. Analysis of the human pancreatic tissue samples revealed that Hic‐5 was overexpressed in patients with CP and was extremely low in healthy pancreas. Hic‐5 was significant up‐regulated in the activated primary PSCs independently from transforming growth factor beta stimulation. CP induced by cerulein injection was ameliorated in Hic‐5 knockout (KO) mice, as shown by staining of tissue level. Simultaneously, the activation ability of the primary PSCs from Hic‐5 KO mice was significantly attenuated. We also found that the Hic‐5 up‐regulation by cerulein activated the NF‐κB (p65)/IL‐6 signalling pathway and regulated the downstream extracellular matrix (ECM) genes such as α‐SMA and Col1a1. Therefore, we determined whether suppressing NF‐κB/p65 alleviated CP by treating mice with the NF‐κB/p65 inhibitor triptolide in the cerulein‐induced CP model and found that pancreatic fibrosis was alleviated by NF‐κB/p65 inhibition. These findings provide evidence for Hic‐5 as a therapeutic target that plays a crucial role in regulating PSCs activation and pancreatic fibrosis. 相似文献
235.
Evans RC Morera-Herreras T Cui Y Du K Sheehan T Kotaleski JH Venance L Blackwell KT 《PLoS computational biology》2012,8(4):e1002493
Calcium through NMDA receptors (NMDARs) is necessary for the long-term potentiation (LTP) of synaptic strength; however, NMDARs differ in several properties that can influence the amount of calcium influx into the spine. These properties, such as sensitivity to magnesium block and conductance decay kinetics, change the receptor's response to spike timing dependent plasticity (STDP) protocols, and thereby shape synaptic integration and information processing. This study investigates the role of GluN2 subunit differences on spine calcium concentration during several STDP protocols in a model of a striatal medium spiny projection neuron (MSPN). The multi-compartment, multi-channel model exhibits firing frequency, spike width, and latency to first spike similar to current clamp data from mouse dorsal striatum MSPN. We find that NMDAR-mediated calcium is dependent on GluN2 subunit type, action potential timing, duration of somatic depolarization, and number of action potentials. Furthermore, the model demonstrates that in MSPNs, GluN2A and GluN2B control which STDP intervals allow for substantial calcium elevation in spines. The model predicts that blocking GluN2B subunits would modulate the range of intervals that cause long term potentiation. We confirmed this prediction experimentally, demonstrating that blocking GluN2B in the striatum, narrows the range of STDP intervals that cause long term potentiation. This ability of the GluN2 subunit to modulate the shape of the STDP curve could underlie the role that GluN2 subunits play in learning and development. 相似文献
236.
237.
Yan Chen Tangjuan Liu Ke Wang Changchun Hou Shuangqi Cai Yingying Huang Zhongye Du Hong Huang Jinliang Kong Yiqiang Chen 《PloS one》2016,11(4)
Biofilm formed by Staphylococcus aureus significantly enhances antibiotic resistance by inhibiting the penetration of antibiotics, resulting in an increasingly serious situation. This study aimed to assess whether baicalein can prevent Staphylococcus aureus biofilm formation and whether it may have synergistic bactericidal effects with antibiotics in vitro. To do this, we used a clinically isolated strain of Staphylococcus aureus 17546 (t037) for biofilm formation. Virulence factors were detected following treatment with baicalein, and the molecular mechanism of its antibiofilm activity was studied. Plate counting, crystal violet staining, and fluorescence microscopy revealed that 32 μg/mL and 64 μg/mL baicalein clearly inhibited 3- and 7-day biofilm formation in vitro. Moreover, colony forming unit count, confocal laser scanning microscopy, and scanning electron microscopy showed that vancomycin (VCM) and baicalein generally enhanced destruction of biofilms, while VCM alone did not. Western blotting and real-time quantitative polymerase chain reaction analyses (RTQ-PCR) confirmed that baicalein treatment reduced staphylococcal enterotoxin A (SEA) and α-hemolysin (hla) levels. Most strikingly, real-time qualitative polymerase chain reaction data demonstrated that 32 μg/mL and 64 μg/mL baicalein downregulated the quorum-sensing system regulators agrA, RNAIII, and sarA, and gene expression of ica, but 16 μg/mL baicalein had no effect. In summary, baicalein inhibited Staphylococcus aureus biofilm formation, destroyed biofilms, increased the permeability of vancomycin, reduced the production of staphylococcal enterotoxin A and α-hemolysin, and inhibited the quorum sensing system. These results support baicalein as a novel drug candidate and an effective treatment strategy for Staphylococcus aureus biofilm-associated infections. 相似文献
238.
Hybrid peptide-polyketide natural products: biosynthesis and prospects toward engineering novel molecules 总被引:2,自引:0,他引:2
The structural and catalytic similarities between modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) inspired us to search for hybrid NRPS-PKS systems. By examining the biochemical and genetic data known to date for the biosynthesis of hybrid peptide-polyketide natural products, we show (1) that the same catalytic sites are conserved between the hybrid NRPS-PKS and normal NRPS or PKS systems, although the ketoacyl synthase domain in NRPS/PKS hybrids is unique, and (2) that specific interpolypeptide linkers exist at both the C- and N-termini of the NRPS and PKS proteins, which presumably play a critical role in facilitating the transfer of the growing peptide or polyketide intermediate between NRPS and PKS modules in hybrid NRPS-PKS systems. These findings provide new insights for intermodular communications in hybrid NRPS-PKS systems and should now be taken into consideration in engineering hybrid peptide-polyketide biosynthetic pathways for making novel "unnatural" natural products. 相似文献
239.
A highly conserved amino acid sequence, GVRAGGGIGD(4831), which may form part of the Ca(2+) release channel pore in RyR2, was subjected to Ala scanning or Ala to Val mutagenesis; function was then measured by expression in HEK-293 cells, followed by Ca(2+) photometry, high affinity [(3)H]ryanodine binding, and single-channel recording. All mutants except I4829A and I4829T (corresponding to the I4897T central core disease mutant in RyR1) displayed caffeine-induced Ca(2+) release in HEK-293 cells; only mutants G4826A, I4829V, and G4830A retained high affinity [(3)H]ryanodine binding; and single-channel function was found for all mutants tested, except for G4822A and A4825V. EC(50) values for caffeine-induced Ca(2+) release were increased for G4822A, R4824A, G4826A, G4828A, and D4831A; decreased for V4823A; and unchanged for A4825V, G4827A, I4829V, and G4830A. Ryanodine (10 microm), which did not stimulate Ca(2+) release in wild type (wt), did so in Ala mutants in amino acids 4823-4827. It inhibited the caffeine response in wt and most mutants, but enhanced the amplitude of caffeine-induced Ca(2+) release in mutant G4828A. It also restored caffeine-induced Ca(2+) release in mutants I4829A and I4829T. In single-channel recordings, mutants I4829V and G4830A retained normal conductance, whereas all others had decreased unitary channel conductances ranging from 27 to 540 picosiemens. Single-channel modulation was retained in G4826A, I4829V, and G4830A, but was lost in other mutants. In contrast to wt and G4826A, I4829V, and G4830A, in which divalent metals were preferentially conducted, mutants with loss of modulation had no selectivity of divalent cations over a monovalent cation. Analysis of Gly(4822) to Asp(4831) mutants in RyR2 supports the view that this highly conserved sequence constitutes part of the ion-conducting pore of the Ca(2+) release channel and plays a key role in ryanodine and caffeine binding and activation. 相似文献
240.
Construction of photodynamic‐effect immunofluorescence probes by a complex of quantum dots,immunoglobulin G and chlorin e6 and their application in HepG2 cell killing 下载免费PDF全文
Zheng‐Yu Yan Li‐Li Wang Meng‐Ying Fei Xin‐Ying Liu Yi‐Long Su Qing‐Qing Du Sheng‐Mei Wu 《Luminescence》2016,31(6):1174-1181
In this study, tri‐functional immunofluorescent probes (Ce6–IgG–QDs) based on covalent combinations of quantum dots (QDs), immunoglobulin G (IgG) and chlorin e6 (Ce6) were developed and their photodynamic ability to induce the death of cancer cells was demonstrated. Strategically, one type of second‐generation photosensitizer, Ce6, was first coupled with anti‐IgG antibody using the EDC/NHS cross‐linking method to construct the photosensitive immunoconjugate Ce6–IgG. Then, a complex of Ce6–IgG–QDs immunofluorescent probes was obtained in succession by covalently coupling Ce6–IgG to water soluble CdTe QDs. The as‐manufactured Ce6–IgG–QDs maintained the bio‐activities of both the antigen–antibody‐based tumour targeting effects of IgG and the photodynamic‐related anticancer activities of Ce6. By way of polyclonal antibody interaction with rabbit anti‐human epidermal growth factor receptor (anti‐EGFR antibody, N‐terminus), Ce6–IgG–QDs were labelled indirectly onto the surface of human hepatocarcinoma (HepG2) cells in cell recognition and killing experiments. The results indicated that the Ce6–IgG–QDs probes have excellent tumour cell selectivity and higher photosensitivity in photodynamic therapy (PDT) compared with Ce6 alone, due to their antibody‐based specific recognition and location of HepG2 cells and the photodynamic effects of Ce6 killed cells based on efficient fluorescence resonance energy transfer between QDs and Ce6. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献