全文获取类型
收费全文 | 70189篇 |
免费 | 2599篇 |
国内免费 | 2966篇 |
出版年
2023年 | 552篇 |
2022年 | 761篇 |
2021年 | 1886篇 |
2020年 | 1064篇 |
2019年 | 1342篇 |
2018年 | 1109篇 |
2017年 | 911篇 |
2016年 | 1428篇 |
2015年 | 3308篇 |
2014年 | 6556篇 |
2013年 | 6226篇 |
2012年 | 4870篇 |
2011年 | 5604篇 |
2010年 | 3990篇 |
2009年 | 3620篇 |
2008年 | 3771篇 |
2007年 | 4069篇 |
2006年 | 2605篇 |
2005年 | 2295篇 |
2004年 | 1491篇 |
2003年 | 1216篇 |
2002年 | 1071篇 |
2001年 | 810篇 |
2000年 | 746篇 |
1999年 | 745篇 |
1998年 | 631篇 |
1997年 | 537篇 |
1996年 | 585篇 |
1995年 | 688篇 |
1994年 | 645篇 |
1993年 | 623篇 |
1992年 | 575篇 |
1991年 | 574篇 |
1990年 | 494篇 |
1989年 | 485篇 |
1988年 | 501篇 |
1987年 | 411篇 |
1986年 | 359篇 |
1985年 | 572篇 |
1984年 | 892篇 |
1983年 | 563篇 |
1982年 | 754篇 |
1981年 | 723篇 |
1980年 | 526篇 |
1979年 | 533篇 |
1978年 | 326篇 |
1977年 | 349篇 |
1976年 | 321篇 |
1974年 | 228篇 |
1973年 | 228篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
《Saudi Journal of Biological Sciences》2017,24(4):875-882
The antimicrobial properties of essential oil from various Santolina species have not been investigated enough in the previous studies dealing with the biological activities of medicinal plants. In Tunisia, Santolina chamaecyparissus L. (Asteraceae) is the only Santolina species recorded and is used as vermifuge and emmenagogue. The chemical composition, antibacterial and antifungal properties of essential oils from the flowerheads and roots of spontaneous S. chamaecyparissus growing in Tunisia and the chemical composition which leads to the Tunisian chemotype are investigated here for the first time. Essential oils isolated by hydro distillation from flowerheads and roots of S. chamaecyparissus were analyzed by GC and GC/MS. Two methods served for antimicrobial assays of the essential oils: diffusion in a solid medium and micro-well dilution assay. Antifungal tests were carried out by the agar incorporation method. Sixty-seven constituents were identified from the essential oil of the flowerhead. The major constituents were: 1,8-cineole and β-eudesmol. Two non identified compounds were present at the highest concentration in root oil. Flowerhead oil was characterized by high contents in monoterpenes and sesquiterpenes oxygenated compounds. The flowerhead essential oil demonstrated potent of antibacterial properties against Pseudomonas aeruginosa ATCC and Enterococcus faecalis ATCC, with MIC of 0.625 μg/ml. These findings demonstrate that the flowerhead essential oils of S. chamaecyparissus have excellent antibacterial properties and for this reason they could contribute to decrease the problem of microbial resistance to antibiotics. 相似文献
2.
3.
4.
5.
6.
Maria Weinert Tharakeswari Selvakumar Travis S. Tierney Kambiz N. Alavian 《Journal of visualized experiments : JoVE》2015,(96)
Degeneration of mesencephalic dopaminergic (mesDA) neurons is the pathological hallmark of Parkinson’s diseae. Study of the biological processes involved in physiological functions and vulnerability and death of these neurons is imparative to understanding the underlying causes and unraveling the cure for this common neurodegenerative disorder. Primary cultures of mesDA neurons provide a tool for investigation of the molecular, biochemical and electrophysiological properties, in order to understand the development, long-term survival and degeneration of these neurons during the course of disease. Here we present a detailed method for the isolation, culturing and maintenance of midbrain dopaminergic neurons from E12.5 mouse (or E14.5 rat) embryos. Optimized cell culture conditions in this protocol result in presence of axonal and dendritic projections, synaptic connections and other neuronal morphological properties, which make the cultures suitable for study of the physiological, cell biological and molecular characteristics of this neuronal population. 相似文献
7.
Abstract Clostridium perfringens alpha-toxin was produced in a protein-hyperproducing strain, Bacillus brevis 47, by cloning the gene into the constructed expression-secretion vector which has the multiple promoters and the signal peptide coding region of an outer cell wall protein gene. The amount of alpha-toxin produced by the B. brevis 47 transformant carrying the gene was approximately 10 times greater than that produced by a B. subtilis transformant carrying the toxin gene. Biological activities and the N-terminal amino acid sequence of the toxin secreted by the B. brevis 47 transformant were identical to those of wild-type alpha-toxin. 相似文献
8.
Abstract. Anopheles stephensi mosquitoes which had fed upon mice infected with Plasmodium yoelii nigeriensis malaria parasites produced significantly fewer eggs than mosquitoes fed on an uninfected mouse. Fecundity reduction was more pronounced when the bloodmeal contained malaria gametocytes and the mosquitoes developed oocysts. Egg production and haematin excretion were correlated for uninfected bloodfed mosquitoes; the presence of P.y. nigeriensis in the blood affected this relationship. Reduced fecundity was associated with a significant reduction of bloodmeal size (measured by haematin excretion) in mosquitoes which ingested gametocytaemic blood. The bloodmeal size in mosquitoes fed on parasitaemic blood without gametocytes was not significantly reduced. The use of haematin assays for determination of bloodmeal size in mosquitoes is discussed. 相似文献
9.
《Bioorganic & medicinal chemistry》2020,28(22):115739
N-phenyl ureidobenzenesulfonates (PUB-SOs) is a new class of promising anticancer agents inducing replication stresses and cell cycle arrest in S-phase. However, the pharmacological target of PUB-SOs was still unidentified. Consequently, the objective of the present study was to identify and confirm the pharmacological target of the prototypical PUB-SO named 2-ethylphenyl 4-(3-ethylureido)benzenesulfonate (SFOM-0046) leading to the cell cycle arrest in S-phase. The antiproliferative and the cytotoxic activities of SFOM-0046 were characterized using the NCI-60 screening program and its fingerprint was analyzed by COMPARE algorithm. Then, human dihydroorotate dehydrogenase (hDHODH) colorimetric assay, uridine rescuing cell proliferation and molecular docking in the brequinar-binding site were performed. As a result, SFOM-0046 exhibited a mean antiproliferative activity of 3.5 μM in the NCI-60 screening program and evidenced that leukemia and colon cancer cell panels were more sensitive to SFOM-0046. COMPARE algorithm showed that the SFOM-0046 cytotoxic profile is equivalent to the ones of brequinar and dichloroallyl lawsone, two inhibitors of hDHODH. SFOM-0046 inhibited the hDHODH in the low nanomolar range (IC50 = 72 nM) and uridine rescued the cell proliferation of HT-29, HT-1080, M21 and MCF-7 cancer cell lines in the presence of SFOM-0046. Finally, molecular docking showed a binding pose of SFOM-0046 interacting with Met43 and Phe62 present in the brequinar-binding site. In conclusion, PUB-SOs and notably SFOM-0046 are new small molecules hDHODH inhibitors triggering replication stresses and S-phase arrest. 相似文献
10.
《Bioorganic & medicinal chemistry》2020,28(11):115492
Effective chemotherapy for solid cancers is challenging due to a limitation in permeation that prevents anticancer drugs from reaching the center of the tumor, therefore unable to limit cancer cell growth. To circumvent this issue, we planned to apply the drugs directly at the center by first collapsing the outer structure. For this, we focused on cell–cell communication (CCC) between N-glycans and proteins at the tumor cell surface. Mature N-glycans establish CCC; however, CCC is hindered when numerous immature N-glycans are present at the cell surface. Inhibition of Golgi mannosidases (GMs) results in the transport of immature N-glycans to the cell surface. This can be employed to disrupt CCC. Here, we describe the molecular design and synthesis of an improved GM inhibitor with a non-sugar mimic scaffold that was screened from a compound library. The synthesized compounds were tested for enzyme inhibition ability and inhibition of spheroid formation using cell-based methods. Most of the compounds designed and synthesized exhibited GM inhibition at the cellular level. Of those, AR524 had higher inhibitory activity than a known GM inhibitor, kifunensine. Moreover, AR524 inhibited spheroid formation of human malignant cells at low concentration (10 µM), based on the disruption of CCC by GM inhibition. 相似文献