全文获取类型
收费全文 | 10342篇 |
免费 | 1173篇 |
国内免费 | 1105篇 |
专业分类
12620篇 |
出版年
2024年 | 29篇 |
2023年 | 136篇 |
2022年 | 366篇 |
2021年 | 518篇 |
2020年 | 463篇 |
2019年 | 494篇 |
2018年 | 518篇 |
2017年 | 393篇 |
2016年 | 484篇 |
2015年 | 677篇 |
2014年 | 773篇 |
2013年 | 772篇 |
2012年 | 898篇 |
2011年 | 804篇 |
2010年 | 555篇 |
2009年 | 454篇 |
2008年 | 546篇 |
2007年 | 474篇 |
2006年 | 436篇 |
2005年 | 344篇 |
2004年 | 353篇 |
2003年 | 362篇 |
2002年 | 352篇 |
2001年 | 242篇 |
2000年 | 158篇 |
1999年 | 180篇 |
1998年 | 107篇 |
1997年 | 94篇 |
1996年 | 89篇 |
1995年 | 92篇 |
1994年 | 68篇 |
1993年 | 55篇 |
1992年 | 54篇 |
1991年 | 46篇 |
1990年 | 40篇 |
1989年 | 42篇 |
1988年 | 26篇 |
1987年 | 20篇 |
1986年 | 18篇 |
1985年 | 8篇 |
1984年 | 12篇 |
1983年 | 14篇 |
1982年 | 13篇 |
1981年 | 11篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1974年 | 2篇 |
1972年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
Hanpeng Liao Yudan Bai Chen Liu Chang Wen Qiue Yang Zhi Chen Samiran Banerjee Shungui Zhou Ville-Petri Friman 《Environmental microbiology》2021,23(12):7483-7496
Composting is widely used to reduce the abundance of antibiotic resistance genes (ARGs) in solid waste. While ARG dynamics have been extensively investigated during composting, the fate and abundance of residual ARGs during the storage remain unexplored. Here, we tested experimentally how ARG and mobile genetic element (MGE) abundances change during compost storage using metagenomics, quantitative PCR and direct culturing. We found that 43.8% of ARGs and 39.9% of MGEs quickly recovered already during the first week of storage. This rebound effect was mainly driven by the regrowth of indigenous, antibiotic-resistant bacteria that survived the composting. Bacterial transmission from the surrounding air had a much smaller effect, being most evident as MGE rebound during the later stages of storage. While hyperthermophilic composting was more efficient at reducing the relative abundance of ARGs and MGEs, relatively greater ARG rebound was observed during the storage of hyperthermophilic compost, exceeding the initial levels of untreated sewage sludge. Our study reveals that residual ARGs and MGEs left in the treated compost can quickly rebound during the storage via airborne introduction and regrowth of surviving bacteria, highlighting the need to develop better storage strategies to prevent the rebound of ARGs and MGEs after composting. 相似文献
102.
Yue Qiu Ding Yuan Ye Wang Jun Wen 《Computer methods in biomechanics and biomedical engineering》2013,16(16):824-833
AbstractThis paper describes a systematic investigation on the hemodynamic environment in a patient-specific AAA with tortuous common iliac artery(CIA) and external iliac artery (EIA). 3D reconstructions from CT scans and subsequent computational simulation are carried out. It is found out that the Newtonian and non-Newtonian models have very similar flow field and WSS distribution. More importantly, it is revealed that the torturous CIA maintained its helical flow. It is concluded that the assumption of Newtonian blood is adequate in capturing the intra-aneurysmal hemodynamics. Moreover, it is speculated that the physiological spiral flow protects the twisted CIA from the thrombosis formation. 相似文献
103.
Qiang Fu Wen Lu Yi-jie Huang Qiang Wu Lin-guang Wang Hai-bo Wang Shu-zhong Jiang Yan-jiong Wang 《Cell biochemistry and biophysics》2013,67(3):911-914
The present study evaluated the efficacy of intracoronary administration of verapamil to attenuate the no-reflow phenomenon following the primary percutaneous coronary intervention (PCI) in patients with the ST-segment elevation acute myocardial infarction (STEMI). A total of 201 patients with STEMI who underwent primary PCI within 12 h from the beginning of the heart attack were included. The no-reflow phenomenon was defined as substantial coronary anterograde flow of TIMI ≤2. Verapamil (100–200 μg) was injected into coronary artery immediately after no-reflow; the coronary arteriography was repeated later. Hundred and ninety-eight patients with STEMI successfully underwent primary PCI, and 246 stents were implanted with the average of 1.2 stents per patient. No-reflow occurred in 25 out of 198 patients (12.6 %). Twenty-one (84 %) patients developed the flow of TIMI ≥3 after intracoronary administration of verapamil, as revealed by repeated coronary angiography. Two patients developed transient hypotension which normalized without treatment within 3–5 min. Three patients showed sinus bradycardia, in one patient there was transient II sinoatrial block, and one patient developed type 1 atrioventricular block. All adverse effects were alleviated after intravenous injection of atropine (0.5–1 mg). In conclusion, the no-reflow phenomenon following primary PCI in patients with STEMI is significantly improved by intracoronary administration of verapamil which is useful to reduce cardiovascular events during operation. 相似文献
104.
Jian Liu Yu Wen Lina Gao Liang Gao Fengjun He Jingxian Zhou 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):72-84
Abstract Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0?nM) and modest anti-proliferative activity (IC50 = 785.8?nM). Through two rounds of optimisation, the indazole derivative 9?u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3?nM) and cellular activity (IC50 = 468.2?nM). Moreover, 9?u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1. 相似文献
105.
Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a binding receptor for hepatitis C virus (HCV). Binding of HCV envelope protein E2 to target cells is a prerequisite to DC-SIGN-mediated signaling. Using cell lines with stable or transient expression of DC-SIGN, we investigated effects of soluble HCV E2 protein on ERK pathway. MEK and ERK are activated by the E2 in NIH3T3 cells stably expressing DC-SIGN. Treatment of the cells with antibody to DC-SIGN results in inhibition of the E2 binding as well as the E2-induced MEK and ERK activation. In HEK293T cells transiently expressing DC-SIGN, activation of MEK and ERK is also induced by the E2. Activation of ERK pathway by HCV E2 through DC-SIGN provides useful information for understanding cellular receptor-mediated signaling. 相似文献
106.
107.
Boosted responsiveness of plant cells to stress at the onset of pathogen‐ or chemically induced resistance is called priming. The chemical β‐aminobutyric acid (BABA) enhances Arabidopsis thaliana resistance to hemibiotrophic bacteria through the priming of the salicylic acid (SA) defence response. Whether BABA increases Arabidopsis resistance to the necrotrophic bacterium Pectobacterium carotovorum ssp. carotovorum (Pcc) is not clear. In this work, we show that treatment with BABA protects Arabidopsis against the soft‐rot pathogen Pcc. BABA did not prime the expression of the jasmonate/ethylene‐responsive gene PLANT DEFENSIN 1.2 (PDF1.2), the up‐regulation of which is usually associated with resistance to necrotrophic pathogens. Expression of the SA marker gene PATHOGENESIS RELATED 1 (PR1) on Pcc infection was primed by BABA treatment, but SA‐defective mutants demonstrated a wild‐type level of BABA‐induced resistance against Pcc. BABA primed the expression of the pattern‐triggered immunity (PTI)‐responsive genes FLG22‐INDUCED RECEPTOR‐LIKE KINASE 1 (FRK1), ARABIDOPSIS NON‐RACE SPECIFIC DISEASE RESISTANCE GENE (NDR1)/HAIRPIN‐INDUCED GENE (HIN1)‐LIKE 10 (NHL10) and CYTOCHROME P450, FAMILY 81 (CYP81F2) after inoculation with Pcc or after treatment with purified bacterial microbe‐associated molecular patterns, such as flg22 or elf26. PTI‐mediated callose deposition was also potentiated in BABA‐treated Arabidopsis, and BABA boosted Arabidopsis stomatal immunity to Pcc. BABA treatment primed the PTI response in the SA‐defective mutants SA induction deficient 2‐1 (sid2‐1) and phytoalexin deficient 4‐1 (pad4‐1). In addition, BABA priming was associated with open chromatin configurations in the promoter region of PTI marker genes. Our data indicate that BABA primes the PTI response upon necrotrophic bacterial infection and suggest a role for the PTI response in BABA‐induced resistance. 相似文献
108.
109.
Jie Liang Bei Zhang Ruo-wu Shen Jia-Bao Liu Mei-hua Gao Ying Li Yuan-Yuan Li Wen Zhang 《PloS one》2013,8(12)
Halofuginone (HF) is an active component of extracts derived from the plant alkaloid febrifugine and has shown therapeutic promise in animal models of fibrotic disease. Our main objectives were to clarify the suppressive effect of HF on concanavalin A (ConA)-induced liver fibrosis. ConA injection into the tail vein caused a great increase in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, while orally administration of HF significantly decreased the levels of the transaminases. In addition, the levels of hyaluronic acid (HA), procollagen III (PCIII) and TGF-β1 in the serum and collagen I, α-SMA, tissue inhibitors of metalloproteinase 2 (TIMP2) and Smad3 in the liver tissue were significantly lowered with the treatment of HF. Histological examination also demonstrated that HF significantly reduced the severity of liver fibrosis. Since ConA-induced liver fibrosis is caused by the repeated activation of T cells, immunomodulatory substances might be responsible for the suppressive effect of HF. We found that the production of nuclear factor (NF)-kB in the serum was increased in ConA-treated group, while decreased significantly with the treatment of HF. The changes of inflammatory cytokines tumor necrosis factor (TNF-α), IL-6 and IL-1β in the serum followed the same rhythm. All together, our findings indicate that orally administration HF (10ppm) would attenuate the liver fibrosis by suppressing the synthesis of collagen I and inflammation-mediated liver injury. 相似文献
110.
Shivanjali Joshi-Barr Jerome V. Karpiak Yogesh Ner Jessica H. Wen Adam J. Engler Adah Almutairi 《Journal of visualized experiments : JoVE》2013,(72)
Complex tissue culture matrices, in which types and concentrations of biological stimuli (e.g. growth factors, inhibitors, or small molecules) or matrix structure (e.g. composition, concentration, or stiffness of the matrix) vary over space, would enable a wide range of investigations concerning how these variables affect cell differentiation, migration, and other phenomena. The major challenge in creating layered matrices is maintaining the structural integrity of layer interfaces without diffusion of individual components from each layer1. Current methodologies to achieve this include photopatterning2-3, lithography4, sequential functionalization5, freeze drying6, microfluidics7, or centrifugation8, many of which require sophisticated instrumentation and technical skills. Others rely on sequential attachment of individual layers, which may lead to delamination of layers9. DGMP overcomes these issues by using an inert density modifier such as iodixanol to create layers of varying densities10. Since the density modifier can be mixed with any prepolymer or bioactive molecule, DGMP allows each scaffold layer to be customized. Simply varying the concentration of the density modifier prevents mixing of adjacent layers while they remain aqueous. Subsequent single step polymerization gives rise to a structurally continuous multilayered scaffold, in which each layer has distinct chemical and mechanical properties. The density modifier can be easily removed with sufficient rinsing without perturbation of the individual layers or their components. This technique is therefore well suited for creating hydrogels of various sizes, shapes, and materials.A protocol for fabricating a 2D-polyethylene glycol (PEG) gel, in which alternating layers incorporate RGDS-350, is outlined below. We use PEG because it is biocompatible and inert. RGDS, a cell adhesion peptide11, is used to demonstrate spatial restriction of a biological cue, and the conjugation of a fluorophore (Alexa Fluor 350) enables us to visually distinguish various layers. This procedure can be adapted for other materials (e.g. collagen, hyaluronan, etc.) and can be extended to fabricate 3D gels with some modifications10. 相似文献