全文获取类型
收费全文 | 2516篇 |
免费 | 203篇 |
国内免费 | 106篇 |
专业分类
2825篇 |
出版年
2024年 | 8篇 |
2023年 | 29篇 |
2022年 | 32篇 |
2021年 | 54篇 |
2020年 | 59篇 |
2019年 | 85篇 |
2018年 | 87篇 |
2017年 | 68篇 |
2016年 | 68篇 |
2015年 | 56篇 |
2014年 | 147篇 |
2013年 | 158篇 |
2012年 | 99篇 |
2011年 | 140篇 |
2010年 | 130篇 |
2009年 | 137篇 |
2008年 | 158篇 |
2007年 | 171篇 |
2006年 | 182篇 |
2005年 | 143篇 |
2004年 | 111篇 |
2003年 | 108篇 |
2002年 | 96篇 |
2001年 | 51篇 |
2000年 | 60篇 |
1999年 | 47篇 |
1998年 | 54篇 |
1997年 | 39篇 |
1996年 | 38篇 |
1995年 | 27篇 |
1994年 | 33篇 |
1993年 | 29篇 |
1992年 | 41篇 |
1991年 | 12篇 |
1990年 | 6篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 1篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 8篇 |
1982年 | 7篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有2825条查询结果,搜索用时 15 毫秒
91.
David Shemesh Naor Bokobza Konstantin Rozenberg Tovit Rosenzweig David Abookasis 《Journal of biophotonics》2019,12(8)
In this study, we use dual‐wavelength optical imaging‐based laser speckle technique to assess cerebral blood flow and metabolic parameters in a mouse model of acute hyperglycemia (high blood glucose). The effect of acute glucose levels on physiological processes has been extensively described in multiple organ systems such as retina, kidney, and others. We postulated that hyperglycemia also alters brain function, which in turn can be monitored optically using dual‐wavelength laser speckle imaging (DW‐LSI) platform. DW‐LSI is a wide‐field, noncontact optical imaging modality that integrates the principles of laser flowmetry and oximetry to obtain macroscopic information such as hemoglobin concentration and blood flow. A total of eight mice (C57/BL6) were used, randomized into two groups of normoglycemia (control, n = 3) and hyperglycemia (n = 5). Hyperglycemia was induced by intraperitoneal injection of a commonly used anesthetic drug combining ketamine and xylazine (KX combo). We found that this KX combo increases blood glucose (BG) levels from 150 to 350 mg/dL, approximately, when measured 18 minutes post‐administration. BG continues to increase throughout the test period, with BG reaching an average of 463 ± 20.34 mg/dL within 60 minutes. BG levels were measured every 10 minutes from tail blood using commercially available glucometer. Experimental results demonstrated reductions in cerebral blood flow (CBF) by 55%, tissue oxygen saturation (SO2) by 15%, and cerebral metabolic rate of oxygen (CMRO2) by 75% following acute hyperglycemia. The observed decrease in these parameters was consistent with results reported in the literature, measured by a variety of experimental techniques. Measurements with laser Doppler flowmetry (LDF) were also performed which confirmed a reduction in CBF following acute hyperglycemia. In summary, our findings indicate that acute hyperglycemia modified brain hemodynamic response and induced significant changes in blood flow and metabolism. As far as we are aware, the implementation of the DW‐LSI to monitor brain hemodynamic and metabolic response to acute hyperglycemia in intact mouse brain has not been previously reported. 相似文献
92.
Palma-Guerrero J Jansson HB Salinas J Lopez-Llorca LV 《Journal of applied microbiology》2008,104(2):541-553
Aims: To investigate the toxic effect of chitosan on important root pathogenic and biocontrol fungi (nematophagous, entomopathogenic and mycoparasitic). Methods and Results: We have used standard bioassays to investigate the effect of chitosan on colony growth and developed bioassays to test spore germination. The results showed that the root pathogenic and mycoparasitic fungi tested were more sensitive to chitosan than nematophagous and entomopathogenic fungi. Chitosanases (and perhaps related enzymes) are involved in the resistance to chitosan. Two fungi, one sensitive to chitosan, Fusarium oxysporum f. sp. radicis‐lycopersici, and one less sensitive, Pochonia chlamydosporia, were selected for ultrastructural investigations. Transmission electron microscopy revealed differences in the ultrastructural alterations caused by chitosan in the spores of the plant pathogenic fungus and in those of the nematophagous fungus. Confocal laser microscopy showed that Rhodamine‐labelled chitosan enters rapidly into conidia of both fungi, in an energy‐dependent process. Conclusions: Nematophagous and entomopathogenic fungi are rather resistant to the toxic effect of chitosan. Resistance of nematophagous and entomopathogenic fungi to chitosan could be associated with their high extracellular chitosanolytic activity. Furthermore, ultrastructural damage is much more severe in the chitosan sensitive fungus. Significance and impact of the study: The results of this paper suggest that biocontrol fungi tested could be combined with chitosan for biological control of plant pathogens and pests. 相似文献
93.
采用CO2激光对12例分布于宫颈、阴道及外阴的子宫内膜异位症病人进行病灶切除碳化治疗,并对其随访了3 ̄7年、无1例复发、局部留下瘢痕。认为外阴子宫内膜异位症采用激光治疗可靠、简便、更优于传统手术治疗。 相似文献
94.
波长514nm的激光照射可用于研究激光导致有丝分裂染色体畸变的效应。本文提供了一种新的辐照系统,能用于研究突变的感应现象,并与从γ-线辐射源获得的结果进行了比较。
Abstract:Laser irradiation at wavelength 514 nm was used to study the effect of lasers in inducing chromosomal aberrations at mitosis.This study offers a new radiation system which could be used for the induction of mutations.Results are compared with those obtained from studies using γ-rays as irradiation source. 相似文献
95.
Oligo-kappa-carrageenans participate as elicitors in the cell-cell recognition process in marine plants. Analytical methods can be usefully applied to gain insight into the biochemistry of these biological processes. Therefore, enzymatically digested oligomers of kappa-carrageenans have been separated and isolated on a Spherisorb ODS1 (250 x 4 mm i.d., particle size 5 microm) column using ion-pair liquid chromatography coupled with an evaporative light scattering detector. Heptylamine (5 mM, pH4) has been selected as the ion-pairing agent and MeOH as the organic modifier in a gradient mode. Overloading the column with 1mg of the mixture, the chromatographic mechanism presented adequate stability. The mobile phase of each isolated oligomer was evaporated and the residue was infused into an electrospray ionisation mass spectrometry (ESIMS) in positive-ion mode with 4:1 MeCN-water as mobile phase. Each ESIMS spectrum presented ions consisting of the oligomer attached with a number of heptylammonium ions depending on the molecule size. In addition, the different m/z values permitted direct detection of the oligomers in ESIMS positive-ion mode. The analytical method developed separated the oligomers up to dotriacontasaccharide. 相似文献
96.
Peng Ni Robert C. VaughanBrady Tragesser Haley HooverC. Cheng Kao 《Journal of molecular biology》2014
Brome mosaic virus (BMV) packages its genomic and subgenomic RNAs into three separate viral particles. BMV purified from barley, wheat, and tobacco have distinct relative abundances of the encapsidated RNAs. We seek to identify the basis for the host-dependent differences in viral RNA encapsidation. Sequencing of the viral RNAs revealed recombination events in the 3′ untranslated region of RNA1 of BMV purified from barley and wheat, but not from tobacco. However, the relative amounts of the BMV RNAs that accumulated in barley and wheat are similar and RNA accumulation is not sufficient to account for the difference in RNA encapsidation. Virions purified from barley and wheat were found to differ in their isoelectric points, resistance to proteolysis, and contacts between the capsid residues and the RNA. Mass spectrometric analyses revealed that virions from the three hosts had different post-translational modifications that should impact the physiochemical properties of the virions. Another major source of variation in RNA encapsidation was due to the purification of BMV particles to homogeneity. Highly enriched BMV present in lysates had a surprising range of sizes, buoyant densities, and distinct relative amounts of encapsidated RNAs. These results show that the encapsidated BMV RNAs reflect a combination of host effects on the physiochemical properties of the viral capsids and the enrichment of a subset of virions. The previously unexpected heterogeneity in BMV should influence the timing of the infection and also the host innate immune responses. 相似文献
97.
98.
Adam P. Silverman 《Journal of molecular biology》2009,385(4):1064-1894
The αvβ3 integrin receptor is an important cancer target due to its overexpression on many solid tumors and the tumor neovasculature and its role in metastasis and angiogenesis. We used a truncated form of the Agouti-related protein (AgRP), a 4-kDa cystine-knot peptide with four disulfide bonds and four solvent-exposed loops, as a scaffold for engineering peptides that bound to αvβ3 integrins with high affinity and specificity. A yeast-displayed cystine-knot peptide library was generated by substituting a six amino acid loop of AgRP with a nine amino acid loop containing the Arg-Gly-Asp integrin recognition motif and randomized flanking residues. Mutant cystine-knot peptides were screened in a high-throughput manner by fluorescence-activated cell sorting to identify clones with high affinity to detergent-solubilized αvβ3 integrin receptor. Select integrin-binding peptides were expressed recombinantly in Pichia pastoris and were tested for their ability to bind to human cancer cells expressing various integrin receptors. These studies showed that the engineered AgRP peptides bound to cells expressing αvβ3 integrins with affinities ranging from 15 nM to 780 pM. Furthermore, the engineered peptides were shown to bind specifically to αvβ3 integrins and had only minimal or no binding to αvβ5, α5β1, and αiibβ3 integrins. The engineered AgRP peptides were also shown to inhibit cell adhesion to the extracellular matrix protein vitronectin, which is a naturally occurring ligand for αvβ3 and other integrins. Next, to evaluate whether the other three loops of AgRP could modulate integrin specificity, we made second-generation libraries by individually randomizing these loops in one of the high-affinity integrin-binding variants. Screening of these loop-randomized libraries against αvβ3 integrins resulted in peptides that retained high affinities for αvβ3 and had increased specificities for αvβ3 over αiibβ3 integrins. Collectively, these data validate AgRP as a scaffold for protein engineering and demonstrate that modification of a single loop can lead to AgRP-based peptides with antibody-like affinities for their target. 相似文献
99.
Ayumu Niida Yoko Kanematsu-Yamaki Tomoko Asakawa Yoshimasa Ishimura Hisashi Fujita Kouta Matsumiya Naoki Nishizawa Yusuke Adachi Taisuke Mochida Kazue Tsuchimori Mariko Yoneyama-Hirozane Junichi Sakamoto Hideki Hirabayashi Hideo Fukui Shiro Takekawa Taiji Asami 《Bioorganic & medicinal chemistry》2018,26(3):566-572
Neuropeptide Y2 receptor (Y2R) agonism is an important anorectic signal and a target of antiobesity drug discovery. Recently, we synthesized a short-length Y2R agonist, PYY-1119 (4-imidazolecarbonyl-[d-Hyp24,Iva25,Pya(4)26,Cha27,36,γMeLeu28,Lys30,Aib31]PYY(23–36), 1) as an antiobesity drug candidate. Compound 1 induced marked body weight loss in diet-induced obese (DIO) mice; however, 1 also induced severe vomiting in dogs at a lower dose than the minimum effective dose administered to DIO mice. The rapid absorption of 1 after subcutaneous administration caused the severe vomiting. Polyethylene glycol (PEG)- and alkyl-modified derivatives of 1 were synthesized to develop Y2R agonists with improved pharmacokinetic profiles, i.e., lower maximum plasma concentration (Cmax) and longer time at maximum concentration (Tmax). Compounds 5 and 10, modified with 20?kDa PEG at the N-terminus and eicosanedioic acid at the Lys30 side chain of 1, respectively, showed high Y2R binding affinity and induced significant body weight reduction upon once-daily administration to DIO mice. Compounds 5 and 10, with their relatively low Cmax and long Tmax, partially attenuated emesis in dogs compared with 1. These results indicate that optimization of pharmacokinetic properties of Y2R agonists is an effective strategy to alleviate emesis induced by Y2R agonism. 相似文献
100.
激光热疗中,激光与生物组织相互作用研究主要包含两方面:光子在生物组织中的迁移规律,以及光生扫热在生物组织在的传导。对前者的描述主要为,基于传输理论的解析法和Monte ̄Carlo模拟,生物组织中光子迁移规律的研究能定量描述组织中的光分布,并进一步获得生物组织中的热分布;考虑到了生物组织特性,所建立了生物组织中温度场分布及变化规律。光子迁移与生物传热理论是研究激光热序不可分割的传热模型,全面描述了生 相似文献