全文获取类型
收费全文 | 2584篇 |
免费 | 233篇 |
出版年
2023年 | 24篇 |
2022年 | 44篇 |
2021年 | 90篇 |
2020年 | 38篇 |
2019年 | 47篇 |
2018年 | 78篇 |
2017年 | 60篇 |
2016年 | 74篇 |
2015年 | 97篇 |
2014年 | 129篇 |
2013年 | 171篇 |
2012年 | 203篇 |
2011年 | 164篇 |
2010年 | 102篇 |
2009年 | 83篇 |
2008年 | 116篇 |
2007年 | 93篇 |
2006年 | 117篇 |
2005年 | 96篇 |
2004年 | 68篇 |
2003年 | 70篇 |
2002年 | 67篇 |
2001年 | 46篇 |
2000年 | 32篇 |
1999年 | 36篇 |
1998年 | 14篇 |
1997年 | 24篇 |
1996年 | 18篇 |
1995年 | 14篇 |
1994年 | 14篇 |
1993年 | 21篇 |
1992年 | 41篇 |
1991年 | 33篇 |
1990年 | 37篇 |
1989年 | 37篇 |
1988年 | 25篇 |
1987年 | 27篇 |
1986年 | 39篇 |
1985年 | 31篇 |
1984年 | 32篇 |
1983年 | 19篇 |
1982年 | 19篇 |
1981年 | 23篇 |
1980年 | 14篇 |
1979年 | 25篇 |
1978年 | 18篇 |
1977年 | 20篇 |
1976年 | 20篇 |
1975年 | 25篇 |
1974年 | 24篇 |
排序方式: 共有2817条查询结果,搜索用时 15 毫秒
151.
Noor Ahmad Shaik Huda M. Al-Kreathy Ghada M. Ajabnoor Prashant Kumar Verma Babajan Banaganapalli 《Saudi Journal of Biological Sciences》2019,26(3):439-448
The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15–40% of non-small cell lung cancer (NSCLC) patients. Although first and second generation anti-EGFR inhibitors are widely used to treat these patients, their therapeutic efficacy is modest and often results in adverse effects or drug resistance. Therefore, there is a need to develop novel as well as safe anti-EGFR drugs. The rapid emergence of computational drug designing provided a great opportunity to both discover and predict the efficacy of novel EGFR inhibitors from plant sources. In the present study, we designed several chemical analogues of edible curcumin (CUCM) compound and assessed their drug likeliness, ADME and toxicity properties using a diverse range of advanced computational methods. We also have examined the structural plasticity and binding characteristics of EGFR wild-type and mutant forms (S769L and K846R) against ligand molecules like Gefitinib, native CUCM, and different CUCM analogues. Through multidimensional experimental approaches, we conclude that CUCM-36 ((1E,4Z,6E)-1-(3,4-Diphenoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-phenoxyphenyl)-1,4,6-heptatrien-3-one) is the best anti-EGFR compound with high drug-likeness, ADME properties, and low toxicity properties. CUCM-36 compound has demonstrated better affinity towards both wild-type (ΔG is ?8.5?kcal/Mol) and mutant forms (V769L & K846R; ΔG for both is >?9.20?kcal/Mol) compared to natural CUCM and Gefitinib inhibitor. This study advises the future laboratory assays to develop CUCM-36 as a novel drug compound for treating EGFR positive non-small cell lung cancer patients. 相似文献
152.
153.
Yumin Dai Ashley N. Peralta Jessica E. Wynn Chringma Sherpa Hao Li Astha Verma Stuart F.J. Le Grice Webster L. Santos 《Bioorganic & medicinal chemistry》2019,27(8):1759-1765
Interaction of HIV-1 rev response element (RRE) RNA with its cognate protein, Rev, is critical for HIV-1 replication. Understanding the mode of interaction between RRE RNA and ligands at the binding site can facilitate RNA molecular recognition as well as provide a strategy for developing anti-HIV therapeutics. Our approach utilizes branched peptides as a scaffold for multivalent binding to RRE IIB (high affinity rev binding site) with incorporation of unnatural amino acids to increase affinity via non-canonical interactions with the RNA. Previous high throughput screening of a 46,656-member library revealed several hits that bound RRE IIB RNA in the sub-micromolar range. In particular, the lead compound, 4B3, displayed a Kd value of 410?nM and demonstrated selectivity towards RRE. A ribonuclease protection assay revealed that 4B3 binds to the stem-loop structure of RRE IIB RNA, which was confirmed by SHAPE analysis with 234 nt long NL4-3 RRE RNA. Our studies further indicated interaction of 4B3 with both primary and secondary Rev binding sites. 相似文献
154.
Dixit Sharma Ankita Sharma Shailender Kumar Verma Birbal Singh 《Journal of molecular recognition : JMR》2019,32(4)
Orientia tsutsugamushi (Ott) is a causative agent of chigger‐borne zoonosis, scrub typhus which is life threatening and highly pervasive illness in humans. In this report, we have mined and classified the proteins involved in pathways unique to Ott by using high‐throughput computational techniques. The 12 metabolic pathways were found to be unique to the pathogen. Forty‐six proteins were reported to be essential for the pathogen's survival and non‐homologous to the humans. The proteins were categorized into different classes, ie, enzymes, transporters, DNA‐binding, secretory, and outer membrane proteins. Further, in silico analysis of 46 proteins showed that 25 proteins were suitable therapeutic targets with known druggable properties. The structural modeling of B3CSG3 (MurA) protein was carried out and catalytic site essential for its functioning was analyzed. Virtual screening of chemical compounds was performed against modeled structure. The docking study by AutodockVina reported compound from PubChem with CID: 16036947 as best and potential inhibitor by means of docking score and binding affinity. The reliability and stability of the MurA‐16036947 complex were confirmed with molecular dynamics simulation. The report will provide insight to understand the mechanism of pathogenesis of Ott and instigate the development of effective treatment strategies against this disease. 相似文献
155.
Vijay Kumar Shalini Gour Nidhi Verma Suman Kumar Kundlik Gadhave Pushpendra Mani Mishra Pankaj Goyal Janmejay Pandey Rajanish Giri Jay Kant Yadav 《Journal of peptide science》2019,25(4)
Seminal amyloids are well known for their role in enhancing HIV infection. Among all the amyloidogenic peptides identified in human semen, PAP248‐286 was found to be the most active and was termed as semen‐derived enhancer of viral infection (SEVI). Although amyloidogenic nature of the peptide is mainly linked with enhancement of the viral infection, the most active physiological conformation of the aggregated peptide remains inconclusive. Lipids are known to modulate aggregation pathway of a variety of proteins and peptides and constitute one of the most abundant biomolecules in human semen. PAP248‐286 significantly differs from the other known amyloidogenic peptides, including Aβ and IAPP, in terms of critical concentration, surface charge, fibril morphology, and structural transition during aggregation. Hence, in the present study, we aimed to assess the effect of a lipid, 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine (DOPC), on PAP248‐286 aggregation and the consequent conformational outcomes. Our initial observation suggested that the presence of the lipid considerably influenced the aggregation of PAP248‐286. Further, ZDOCK and MD simulation studies of peptide multimerization have suggested that the hydrophobic residues at C‐terminus are crucial for PAP248‐286 aggregation and are anticipated to be major DOPC‐interacting partners. Therefore, we further assessed the aggregation behaviour of C‐terminal (PAP273‐286) fragment of PAP248‐286 and observed that DOPC possesses the ability to interfere with the aggregation behaviour of both the peptides used in the current study. Mechanistically, we propose that the presence of DOPC causes considerable inhibition of the peptide aggregation by interfering with the peptide's disordered state to β‐sheet transition. 相似文献
156.
Marie Paul Audrey Mayi David Forfuet Foncha Cyril Kowo Timoleon Tchuinkam Katherine Brisco Damian Nota Anong Sehgal Ravinder Anthony John Cornel 《Journal of vector ecology》2019,44(2):271-281
Deforestation is a major threat to biodiversity but little data exist on how deforestation in real‐time affects the overall mosquito species community despite its known role in the transmission of diseases. We compared the abundance and diversity of Culex mosquitoes before and after deforestation along a gradient of three different anthropogenic disturbance levels in a tropical rainforest in southwestern Cameroon. The collections were conducted in unlogged forest (January, 2016), selectively logged forest (January, 2017), and within a young palm plantation (October, 2017) using net traps, sweep nets, resting traps, and dipping for immature stages in water bodies. Mosquitoes were morphologically identified to subspecies, groups, and species. A total of 2,556 mosquitoes was collected of which 1,663 (65.06%) belong to the genus Culex, (n=427 (25.68%) in the unlogged forest; n=900 (54.12%) in the selectively logged forest; and n=336 (20.2%) in the young palm plantation) with a significant difference among the habitats. Diversity and richness of mosquitoes varied significantly among habitats with the highest values found in the selectively logged forest (H=2.4; DS=0.87; S=33) and the lowest value in the unlogged forest (H=1.37; DS=0.68; S=13). The results of this study showed that deforestation affects the abundance and diversity of Culex mosquitoes and favors the invasion of anthropophilic mosquitoes. Higher mosquito abundance and diversity in the selectively logged forest than in the pristine forest is notable and some explanations for these differences are discussed. 相似文献
157.
158.
Garsa Anita Kumari Choudhury Prasanta Kumar Puniya Anil Kumar Dhewa Tejpal Malik Ravinder Kumar Tomar Sudhir Kumar 《Probiotics and antimicrobial proteins》2019,11(4):1403-1413
Probiotics and Antimicrobial Proteins - Bovicin is a type AII lantibiotic, possessing two β-methyllanthionine and a disulfide bridge encoded by bovA gene hitherto unknown a couple of decades... 相似文献
159.
Lijuan Sun Sanjay Verma Navin Michael Siew Pang Chan Jianhua Yan Suresh Anand Sadananthan Stefan G. Camps Hui Jen Goh Priya Govindharajulu John Totman David Townsend Julian Pak‐Nam Goh Lei Sun Bernhard Otto Boehm Su Chi Lim Siew Kwan Sze Christiani Jeyakumar Henry Houchun Harry Hu S. Sendhil Velan Melvin Khee‐Shing Leow 《Obesity (Silver Spring, Md.)》2019,27(9):1434-1442
160.