全文获取类型
收费全文 | 7474篇 |
免费 | 459篇 |
国内免费 | 20篇 |
出版年
2024年 | 14篇 |
2023年 | 102篇 |
2022年 | 278篇 |
2021年 | 411篇 |
2020年 | 377篇 |
2019年 | 561篇 |
2018年 | 443篇 |
2017年 | 310篇 |
2016年 | 393篇 |
2015年 | 410篇 |
2014年 | 504篇 |
2013年 | 640篇 |
2012年 | 607篇 |
2011年 | 593篇 |
2010年 | 311篇 |
2009年 | 274篇 |
2008年 | 297篇 |
2007年 | 294篇 |
2006年 | 256篇 |
2005年 | 210篇 |
2004年 | 166篇 |
2003年 | 115篇 |
2002年 | 104篇 |
2001年 | 18篇 |
2000年 | 14篇 |
1999年 | 19篇 |
1998年 | 21篇 |
1997年 | 16篇 |
1996年 | 16篇 |
1995年 | 6篇 |
1994年 | 10篇 |
1993年 | 13篇 |
1992年 | 6篇 |
1991年 | 14篇 |
1990年 | 6篇 |
1989年 | 11篇 |
1988年 | 8篇 |
1987年 | 12篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 13篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1976年 | 3篇 |
1974年 | 7篇 |
1973年 | 3篇 |
1963年 | 2篇 |
1962年 | 2篇 |
排序方式: 共有7953条查询结果,搜索用时 15 毫秒
31.
Mohammad B. Rashid Katsuhiko Shirahige Naotake Ogasawara Hiroshi Yoshikawa 《Gene》1994,150(2):213-220
We have analyzed the relationship between autonomously replicating sequence (ARS) structure and function for three ARS (ARS605, ARS607 and ARS609) from chromosome VI of Saccharomyces cerevisiae by systematic XhoI-linker mutation in the ARS consensus sequence (ACS) and flanking sequences. All mutations that encroached upon the ACS destroyed ARS activity. DNA sequences stimulative for ARS function were identified on either side of the ACS of ARS605 and only on the 3'-side of the ACS of ARS607. In ARS609, however, no such stimulative sequences were observed. Base substitutions complementary to the wild-type sequence of those stimulative regions, in ARS605 and ARS607, that did not change the AG of unwinding nor affected ARS activity suggests that these regions have, at least, a function as DNA-unwinding elements (DUE). ARS605, ARS607 and ARS609 DNA are of low AG value and showed hypersensitivity to single-strand-specific nuclease when inserted in negatively supercoiled plasmid. Linker mutations inhibitory for ARS activity (5L11 and 7L14) also caused significant changes in local nucleotide (nt) sensitivity within the ACS and its adjoining regions. Complementary base substitutions, however, did not affect these changes in local nt sensitivity. These results imply that the stimulative regions flanking the ACS are necessary to produce an optimum conformation around the ACS which may be important for full ARS activity. 相似文献
32.
33.
Mohsen A. F. El-Hazmi Hassan M. Bahakim Arjumand S. Warsy Abdulkarim Al-Momen Abdullah Al-Wazzan Ibrahim Al-Fawwaz Sameer Huraib Mohammad Harakati 《Molecular and cellular biochemistry》1993,124(1):17-22
Sickle cell anaemia (SCA) exhibits significant variations in clinical presentation in different populations for which several genetic factors including SCA-associated -and -thalassaemias, G-6-PD deficiency and elevated Hb F level have been implicated as possible ameliorating factors. Saudi Arabia is unique in that mild and severe forms of the disease occur at a high frequency. We investigated the G/A ratio and Hb F level and correlated these values with the severity of SCA. The results showed that Hb F level varies significantly in both groups of patients with no evident correlation with the mild clinical manifestations. However, G/A ratio correlated significantly with the disease severity where a high ratio was observed in patients with the mild and a low ratio in patients with the severe disease. The results are evaluated and discussed in the light of correlation studies and regression analysis. 相似文献
34.
Seyede Saba Hosseini Seyed Omar Ebrahimi Maryam Haji Ghasem Kashani Somayeh Reiisi 《Cell biology international》2023,47(1):98-109
Naturally-derived drugs have drawn much attention in recent decades. Efficiency, lower toxicity, and economic reasons are some of their advantages that justify this broad range of administration for different diseases, including cancer. If we can find a specific combination that boosts the effects of their single therapy, leading to synergism effect, increased efficiency, and decreased toxicity, they can act even better. Quercetin and fisetin, two well-known flavonoids, have been used to fight against various cancers. In this study, we investigated their possible synergism quercetin and fisetin on MCF7, MDA-MB-231, BT549, T47D, and 4T1 breast cancer cell lines. Then the optimum combined dose was used to study their impacts on wound healing abilities and clonogenic properties. The real-time qPCR was used to study the expression of their validated downstream effectors in predicted pathways. A significant synergism effect (p < .01, combination index: <1) was observed for all cell lines. Combination therapy was significantly more effective in colony formation (p < .0001) and wound healing assays (p < .001) compared to single therapies. The expression level of potential effectors was also showed a greater change. In vivo study confirmed the in vitro results and showed how significantly (p < .001) their synergism promotes their singular function in inhibiting cancer progression. The breast cancer mouse models receiving combined therapy lived longer with higher average body weight and smaller tumor sizes. These results exhibit that quercetin and fisetin inhibit cancer cell proliferation, migration and colony formation synergistically, and matrix metalloproteinase signaling and apoptotic pathways are relatively responsible for inhibitory activities. 相似文献
35.
The online photoreaction of the rose bengal photosensitized luminol–copper (II) chemiluminescence (CL) system was used for the determination of β-nicotinamide adenine dinucleotide (NADH) and ethanol (EtOH) in pharmaceutical formulations combined with a flow injection technique. NADH can significantly enhance the CL emission of the reaction. For EtOH, alcohol dehydrogenase in soluble form was utilized in the presence of nicotinamide adenine dinucleotide resulting in NADH production. The limit of detection (3σ blank, 𝑛 = 3) of 4.0 × 10−8 and 2.17 × 10−5 M, and linear range 1.3 × 10−7 to 2.5 × 10−5 M (R2 = 0.9998, n = 6) and 0.11–2.17 × 10−3 M (R2 = 0.9996, n = 6) were obtained for NADH and EtOH respectively. The injection rate was 100 h−1 with a relative standard deviation (n = 3) of 1.5–4.8% in the range studied for both analytes. The procedure was satisfactorily applied to pharmaceutical formulations with recoveries in the range 91.6 ± 3.0% to 110 ± 2.0% for NADH and 88 ± 3.0% to 95.4 ± 4.0% for EtOH. The results obtained were very consistent and did not differ considerably from the reported approaches at a 95% confidence limit. The possible mechanism of the CL reaction is also explained briefly. 相似文献
36.
Huwida A. A. Abdel-Kader Naeima Yousef Mohammad Anwar Hossain Mona F. A. Dawood 《Phyton》2023,92(7):1955-1974
The extensive use of nanoparticles (NPs) in diverse applications causes their localization to aquatic habitats,
affecting the metabolic products of primary producers in aquatic ecosystems, such as algae. Synthesized calcium
oxide nanoparticles (CaO NPs) are of the scarcely studied NPs. Thus, the current work proposed that the exposure to CaO NPs may instigate metabolic pathway to be higher than that of normally growing algae, and positively
stimulate algal biomass. In this respect, this research was undertaken to study the exposure effect of CaO NPs (0,
20, 40, 60, 80, and 100 µg mL−1
) on the growth, photosynthesis, respiration, oxidative stress, antioxidants, and
lipid production of the microalga Coccomyxa chodatii SAG 216-2. The results showed that the algal growth concomitant with chlorophyll content, photosynthesis, and calcium content increased in response to CaO NPs. The
contents of biomolecules such as proteins, amino acids, and carbohydrates were also promoted by CaO NPs with
variant degrees. Furthermore, lipid production was enhanced by the applied nanoparticles. CaO NPs induced the
accumulation of hydrogen peroxide, while lipid peroxidation was reduced, revealing no oxidative behavior of the
applied nanoparticles on alga. Also, CaO NPs have a triggering effect on the antioxidant enzymes such as superoxide dismutase, catalase, ascorbate peroxidase, and guaiacol peroxidase. The results recommended the importance of the level of 60 µg mL−1 CaO NPs on lipid production (with increasing percentage of 65% compared
to control) and the highest dry matter acquisition of C. chodatii. This study recommended the feasibility of an
integrated treatment strategy of CaO NPs in augmenting biomass, metabolic up-regulations, and lipid accumulation in C. chodatii. 相似文献
37.
Anticancer potential of Ferula assa-foetida and its constituents,a powerful plant for cancer therapy
Mohammad Amin Ghaffari Sirizi Jalil Alizadeh Ghalenoei Mohammad Allahtavakoli Hasan Forouzanfar Seyyed Majid Bagheri 《World journal of biological chemistry》2023,14(2):28-39
Cancer is one of the main challenges of the health system around the world. This disease is increasing in developing countries and imposes heavy costs on patients and governments. On the other hand, despite various drugs, the death rate among cancer patients is still high and the current treatments have many harmful effects. In the traditional medicine of different countries, there are many medicinal plants that can be effective in the treatment of cancer. Ferula plants are traditionally used as spices and food or for medicinal purposes. Ferula assa-foetida is one of the famous plants of this genus, which has been used for the treatment of various diseases since ancient times. Among the main compounds of this plant, we can mention monoterpenes, sulfide compounds and polyphenols, which can show different therapeutic effects. This article has been compiled with the aim of collecting evidence and articles related to the anti-cancer effects of extracts, derived compounds, essential oils and nanoparticles containing Ferula assa-foetida. This review article was prepared by searching the terms Ferula assa-foetida and cancer, and relevant information was collected through searching electronic databases such as ISI Web of Knowledge, PubMed, and Google Scholar. Fort unately, the results of this review showed that relatively comprehensive studies have been conducted in this field and shown that Ferula assa-foetida can be very promising in the treatment of cancer. 相似文献
38.
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
39.
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
40.
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