全文获取类型
收费全文 | 6802篇 |
免费 | 401篇 |
国内免费 | 21篇 |
出版年
2023年 | 94篇 |
2022年 | 132篇 |
2021年 | 338篇 |
2020年 | 338篇 |
2019年 | 489篇 |
2018年 | 374篇 |
2017年 | 265篇 |
2016年 | 355篇 |
2015年 | 384篇 |
2014年 | 475篇 |
2013年 | 607篇 |
2012年 | 563篇 |
2011年 | 557篇 |
2010年 | 294篇 |
2009年 | 255篇 |
2008年 | 280篇 |
2007年 | 279篇 |
2006年 | 248篇 |
2005年 | 201篇 |
2004年 | 152篇 |
2003年 | 116篇 |
2002年 | 100篇 |
2001年 | 24篇 |
2000年 | 18篇 |
1999年 | 20篇 |
1998年 | 24篇 |
1997年 | 17篇 |
1996年 | 17篇 |
1995年 | 7篇 |
1994年 | 9篇 |
1993年 | 17篇 |
1992年 | 9篇 |
1991年 | 14篇 |
1990年 | 6篇 |
1989年 | 12篇 |
1988年 | 7篇 |
1987年 | 14篇 |
1986年 | 14篇 |
1985年 | 13篇 |
1984年 | 14篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 9篇 |
1979年 | 3篇 |
1978年 | 5篇 |
1976年 | 6篇 |
1975年 | 3篇 |
1974年 | 7篇 |
1973年 | 4篇 |
排序方式: 共有7224条查询结果,搜索用时 640 毫秒
41.
Aysan Etemadi Salar Hemmati Mohammad Shahrivar-Gargari Yasaman Tamaddon Abibiglue Ahad Bavili Maryam Hamzeh-Mivehroud Siavoush Dastmalchi 《化学与生物多样性》2023,20(8):e202300075
Indanone derivatives containing meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC50 values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC50 value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC50=0.04 μM). Structure-activity relationship (SAR) analysis revealed that there is no significant difference between meta and para-substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta-substituted compounds, while the most active BChE inhibitor is para-substituted derivative 7 b . The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone-aminopropoxy benzylidenes could be used in drug-discovery against Alzheimer's disease. 相似文献
42.
This study aimed to assess the anthelmintic activity of methanol extracts from Merremia vitifolia stems using a combination approach encompassing experimental, in vitro, and in silico evaluations. Despite the well-recognized pharmacological properties of M. vitifolia, its potential as an anthelmintic agent remained unexplored. This plant's anthelmintic potential was assessed on adult earthworms (Pheretima posthuma), revealing a dose-dependent reduction in spontaneous motility leading to paralysis and eventual mortality. The most effective dose of M. vitifolia (200 mg/ml) for anthelmintic effects on Pheretima posthuma was identified. Complementary in silico investigations were also conducted, employing Autodock PyRx 0.8 for docking studies of reported M. vitifolia compounds. Notably, quercetin emerged as a promising candidate with superior binding energies against β-tubulin (−8.3 Kcal/mol). Moreover, this comprehensive research underlines the anthelmintic potential of Merremia vitifolia stem extract and highlights quercetin as a noteworthy compound for further investigation in the quest for novel anthelmintic agents. 相似文献
43.
Nagib Ahsan Luca Fornelli Fares Z. Najar Sanjeewa Gamagedara Mohammad Robiul Hossan R. Shyama Prasad Rao Ujwal Punyamurtula Andrew Bauer Zhibo Yang Steven B. Foster Maureen A. Kane 《Proteomics》2023,23(20):2300150
Blood serum is arguably the most analyzed biofluid for disease prediction and diagnosis. Herein, we benchmarked five different serum abundant protein depletion (SAPD) kits with regard to the identification of disease-specific biomarkers in human serum using bottom-up proteomics. As expected, the IgG removal efficiency among the SAPD kits is highly variable, ranging from 70% to 93%. A pairwise comparison of database search results showed a 10%–19% variation in protein identification among the kits. Immunocapturing-based SAPD kits against IgG and albumin outperformed the others in the removal of these two abundant proteins. Conversely, non-antibody-based methods (i.e., kits using ion exchange resins) and kits leveraging a multi-antibody approach were proven to be less efficient in depleting IgG/albumin from samples but led to the highest number of identified peptides. Notably, our results indicate that different cancer biomarkers could be enriched up to 10% depending on the utilized SAPD kit compared with the undepleted sample. Additionally, functional analysis of the bottom-up proteomic results revealed that different SAPD kits enrich distinct disease- and pathway-specific protein sets. Overall, our study emphasizes that a careful selection of the appropriate commercial SAPD kit is crucial for the analysis of disease biomarkers in serum by shotgun proteomics. 相似文献
44.
Roger S. McIntyre Mohammad Alsuwaidan Bernhard T. Baune Michael Berk Koen Demyttenaere Joseph F. Goldberg Philip Gorwood Roger Ho Siegfried Kasper Sidney H. Kennedy Josefina Ly-Uson Rodrigo B. Mansur R. Hamish McAllister-Williams James W. Murrough Charles B. Nemeroff Andrew A. Nierenberg Joshua D. Rosenblat Gerard Sanacora Alan F. Schatzberg Richard Shelton Stephen M. Stahl Madhukar H. Trivedi Eduard Vieta Maj Vinberg Nolan Williams Allan H. Young Mario Maj 《World psychiatry》2023,22(3):394-412
Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population. 相似文献
45.
46.
Effect of pH and calcium on short-term NO3- fluxes in roots of barley seedlings 总被引:1,自引:0,他引:1 下载免费PDF全文
The effect of pH and Ca2+ on net NO3- uptake, influx, and efflux by intact roots of barley (Hordeum vulgare L.) seedlings was studied. Seedlings were induced with NO3- or NO2-. Net NO3- uptake and efflux, respectively, were determined by following its depletion from, and accumulation in, the external solution. Since roots of both uninduced and NO2(-)-induced seedlings contain little internal NO3- initial net uptake rates are equivalent to influx (M. Aslam, R.L. Travis, R.C. Huffaker [1994] Plant Physiol 106: 1293-1301). NO3-, uptake (influx) by these roots was little affected at acidic pH. In contrast, in NO3(-)-induced roots, which accumulate NO3-, net uptake rates decreased in response to acidic pH. Under these conditions, NO3- efflux was stimulated and was a function of root NO3- concentration. Conversely, at basic pH, NO3- uptake by NO3- and NO2(-)-induced and uninduced roots decreased, apparently because of the inhibition of influx. Calcium had little effect on NO3- uptake (influx) by NO2(-)-induced roots at either pH 3 or 6. However, in NO3(-)-induced roots, lack of Ca2+ at pH 3 significantly decreased net NO3- uptake and stimulated efflux. The results indicate that at acidic pH the decrease in net NO3- uptake is due to the stimulation of efflux, whereas at basic pH, it is due to the inhibition of influx. 相似文献
47.
Hamid Rashid Mohammad Najmus Saqib Abdul Aala Rajoka Muhammad Ibrahim Siddiqui Khawar Sohail 《Biotechnology Techniques》1997,11(4):245-248
A simple, sensitive, accurate and more informative assay for determining the number of modified groups during the course of carboxyl group modification is described. Monomeric carboxymethylcellulase (CMCase) from Aspergillus niger was modified by 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (EDC) in the presence of glycinamide. The different time-course aliquots were subjected to non-denaturing PAGE and the gel stained for CMCase activity. The number of carboxyl groups modified are directly read from the ladder of the enzyme bands developed at given time. This method showed that after 75 min of modification reaction there were five major species of modified CMCases in which 6 to 10 carboxyls were modified. 相似文献
48.
In this paper we describe a fast and mild method based on the use of a unique cation exchanger and buffers containing ethylene glycol and salt for the purification of the myelin basic protein (MBP; MW 18.5 kDa). MBP thus purified hydrolyses catalytically p-nitrophenyl acetate. This esterase activity facilitates not only the purification of MBP but also indicates that probably it is in its native state, i.e. there is a good chance that the purified molecules are structurally and chemically identical. This is a prerequisite to obtain crystals appropriate for x-ray diffraction and other studies.Abbreviations used MBP
myelin basic protein
- MW
molecular weight
- kDa
kilo Dalton
- octyl-POE
n-octylpolydisperse oligooxyethylene
- CHAPS
3-3-cholamidopropyl dimethylammonio-1-propane-sulfonate
- CTAB
cetyltrimethylammonium bromide
- SDS
sodium dodecyl sulfate
- SDS-PAGE
polyacrylamide gel electrophoresis in the presence of SDS
- G 3707
heptaoxyethylene lauryl ether
- TWEEN-20
polyoxyethylenesorbitan-monolaurat
- EDTA
ethylenediaminetetraacetic acid
- HEPES
N-(2-hydroxyethyl)-piperazine-N-(2-ethanesulfonic acid) 相似文献
49.
50.
Nabil Elsayed Allen Hacker Mohammad Mustafa Klaus Kuehn Gerhard Schrauzer 《Biochemical and biophysical research communications》1982,104(2):564-569
The effects of reducing glutathione peroxidase activity in the lung by changing dietary selenium intake has been investigated. In animals that were exposed to room air, selenium effects were confined to glutathione peroxidase activity, whereas under conditions of oxidant stress (ozone) the decrease in glutathione peroxidase activity prevented the stimulation of the pentose phosphate cycle (assayed by measuring glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities) which has been reported to increase in response to oxidant stress. The suppression of glutathione peroxidase activity was found to depend on dietary selenium concentration. The physiological significance of this observation may be related to the process of injury and repair in the lung. 相似文献