全文获取类型
收费全文 | 969篇 |
免费 | 52篇 |
出版年
2023年 | 6篇 |
2022年 | 16篇 |
2021年 | 26篇 |
2020年 | 28篇 |
2019年 | 53篇 |
2018年 | 28篇 |
2017年 | 16篇 |
2016年 | 34篇 |
2015年 | 23篇 |
2014年 | 35篇 |
2013年 | 51篇 |
2012年 | 65篇 |
2011年 | 50篇 |
2010年 | 36篇 |
2009年 | 35篇 |
2008年 | 61篇 |
2007年 | 43篇 |
2006年 | 44篇 |
2005年 | 25篇 |
2004年 | 37篇 |
2003年 | 43篇 |
2002年 | 17篇 |
2001年 | 30篇 |
2000年 | 15篇 |
1999年 | 7篇 |
1998年 | 7篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1992年 | 10篇 |
1991年 | 5篇 |
1990年 | 7篇 |
1989年 | 12篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 10篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 9篇 |
1968年 | 3篇 |
1964年 | 6篇 |
1961年 | 5篇 |
1959年 | 5篇 |
排序方式: 共有1021条查询结果,搜索用时 62 毫秒
191.
Lung cancer is the leading cause of cancer deaths worldwide among both men and women, with more than 1 million deaths annually. Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers.Although recent advances have been made in diagnosis and treatment strategies, the prognosis of NSCLC patients is poor and it is basically due to a lack of early diagnostic tools.However, in the last years genetic and biochemical studies have provided more information about the protein and gene's mutations involved in lung tumors. Additionally, recent proteomic and microRNA's approaches have been introduced to help biomarker discovery.Here we would like to discuss the most recent discoveries in lung cancer pathways, focusing on the genetic and epigenetic factors that play a crucial role in malignant cell proliferation, and how they could be helpful in diagnosis and targeted therapy. 相似文献
192.
Emond S André I Jaziri K Potocki-Véronèse G Mondon P Bouayadi K Kharrat H Monsan P Remaud-Simeon M 《Protein science : a publication of the Protein Society》2008,17(6):967-976
Amylosucrase is a transglucosidase that catalyzes amylose-like polymer synthesis from sucrose substrate. About 60,000 amylosucrase variants from two libraries generated by the MutaGen random mutagenesis method were submitted to an in vivo selection procedure leading to the isolation of more than 7000 active variants. These clones were then screened for increased thermostability using an automated screening process. This experiment yielded three improved variants (two double mutants and one single mutant) showing 3.5- to 10-fold increased half-lives at 50 degrees C compared to the wild-type enzyme. Structural analysis revealed that the main differences between wild-type amylosucrase and the most improved variant (R20C/A451T) might reside in the reorganization of salt bridges involving the surface residue R20 and the introduction of a hydrogen-bonding interaction between T451 of the B' domain and D488 of flexible loop 8. This double mutant is the most thermostable amylosucrase known to date and the only one usable at 50 degrees C. At this temperature, amylose synthesis by this variant using high sucrose concentration (600 mM) led to the production of amylose chains twice as long as those obtained by the wild-type enzyme at 30 degrees C. 相似文献
193.
Glucosidation of the new 8-amino-6-benzyl(or substituted benzyl)-2,8-dihydro-1,2,4-triazolo[4,3-b][1,2,4]triazin-7(3H)-ones (3a-d) with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide 4 gave the corresponding N-glucosides 5a-d. Chemical transformations leading to new functionalities have also been achieved to give compounds 7-12. Antimicrobial activity of compounds 5a-c against Aspergillus fumigatus, Penicillium italicum, Syncephalastrum racemosum, Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli is described. 相似文献
194.
Ahsan Mushir Shemsi Firdous Ahmad Khanday Ahsanulhaq Qurashi Amjad Khalil Gea Guerriero Khawar Sohail Siddiqui 《Biotechnology advances》2019,37(3):357-381
Numerous enzymes of biotechnological importance have been immobilized on magnetic nanoparticles (MNP) via random multipoint attachment, resulting in a heterogeneous protein population with potential reduction in activity due to restriction of substrate access to the active site. Several chemistries are now available, where the modifier can be linked to a single specific amino acid in a protein molecule away from the active-site, thus enabling free access of the substrate. However, rarely these site-selective approaches have been applied to immobilize enzymes on nanoparticles. In this review, for the first time, we illustrate how to adapt site-directed chemical modification (SDCM) methods for immobilizing enzymes on iron-based MNP. These strategies are mainly chemical but may additionally require genetic and enzymatic methods. We critically examine each method and evaluate their scope for simple, quick, efficient, mild and economical immobilization of enzymes on MNP. The improvements in the catalytic properties of few available examples of immobilized enzymes are also discussed. We conclude the review with the applications and future prospects of site-selectively modified magnetic enzymes and potential benefits of this technology in improving enzymes, including cold-adapted homologues, modular enzymes, and CO2-sequestering, as well as non-iron based nanomaterials. 相似文献
195.
Naheed N Kaderbhai Khalil Ahmed Mustak A Kaderbhai 《Protein science : a publication of the Protein Society》2010,19(7):1344-1353
A chimeric mammalian globular cytochrome b5 fused to Escherichia coli alkaline phosphatase signal sequence (SS) was used as a model probe to investigate the influence of substituting each one of the standard 20 amino acids at its N‐terminus on the Sec‐dependent export of the precursor to the periplasmic space of E. coli. Substituting the native Met+1 of the passenger protein flanking the SS with any one of the remaining 19 amino acids introduced significant changes in the export of cytochrome b5 without jamming the Sec‐dependent translocon. Acidic and hydrophilic residues proved to be the most efficient promoters of export. Small, nonbulky and basic residues yielded intermediate levels of the hemoprotein export. Replacement with a Cys+1 residue generated significant quantities of both monomeric and disulfide‐linked dimeric forms. However, bulky, aromatic and hydrophobic residues caused a significant decline in the rates of secretion. In expectation with their absences in the natural periplasmically secreted proteins, Pro and Ile‐tagged cytochrome b5 precursors failed to generate any detectable secreted recombinant products. Although Ala, amongst the native E. coli periplasmic proteins, is the preferred X+1 residue with an occurrence of 50% frequency, it proved half as effective in promoting export when inserted proximally to the SS of cytochrome b5. The mechanisms involved for these export variations are discussed. The findings will prove beneficial for high‐level generation of recombinant proteins by secretory means for pharmaceutical and related biotechnological applications. 相似文献
196.
Ovais Muhammad Ahmad Irshad Khalil Ali Talha Mukherjee Sudip Javed Rabia Ayaz Muhammad Raza Abida Shinwari Zabta Khan 《Applied microbiology and biotechnology》2018,102(10):4305-4318
Applied Microbiology and Biotechnology - Nanotechnology has emerged as a prominent scientific discipline in the technological revolution of this millennium. The scientific community has focused on... 相似文献
197.
Meligy Fatma Y. Elgamal Dalia A. Abd Allah Eman S. H. Idriss Naglaa K. Ghandour Nagwa M. Bayoumy Ehab M. R. Khalil Azza Sayed Abdelrehim El Fiky Mohamed M. Elkhashab Mostafa 《Molecular biology reports》2019,46(6):5841-5858
Molecular Biology Reports - Parkinson’s disease (PD) is a chronic neurodegenerative disease. Unfortunately, the effectiveness of anti-Parkinson treatments gradually diminishes owing to the... 相似文献
198.
199.
Sayed M. Riyadh Shojaa A. El‐Motairi Hany E. A. Ahmed Khaled D. Khalil EL‐Sayed E. Habib 《化学与生物多样性》2018,15(9)
2‐(1‐{4‐[(4‐Methylphenyl)sulfonamido]phenyl}ethylidene)thiosemicarbazide ( 3 ) was exploited as a starting material for the synthesis of two novel series of 5‐arylazo‐2‐hydrazonothiazoles 6a – 6j and 2‐hydrazono[1,3,4]thiadiazoles 10a – 10d , incorporating sulfonamide group, through its reactions with appropriate hydrazonoyl halides. The structures of the newly synthesized products were confirmed by spectral and elemental analyses. Also, the antimicrobial, anticancer, and DHFR inhibition potency for two series of thiazoles and [1,3,4]thiadiazoles were evaluated and explained by molecular docking studies and SAR analysis. 相似文献
200.
Kehinde O. Erinle Zhao Jiang Bingbing Ma Khalil Ur-Rehman Andleeb Shahla 《International journal of phytoremediation》2018,20(4):343-351
Pearl millet has been recommended beneficial for several therapeutic purposes. However, little is known of the physiological responses to abiotic stressors, especially of atrazine. In order to elucidate the physiological and molecular responses of pearl millet to atrazine stress, we studied the response of various biomarkers under increasing herbicide concentrations (0, 5, 10, and 50 mg/kg). We also quantified the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (H2O2 and O2??) produced in the leaves to evaluate the extent of oxidative damage. Increasing atrazine concentrations significantly increased ROS and MDA production in the plant leaves. Ascorbate peroxidase (APX) and peroxidase (POD) activities increased, while catalase (CAT) and superoxide dismutase activities reduced with increasing atrazine concentrations. Generally, atrazine applied at 50 mg/kg suppressed chlorophyll contents, whereas, chlorophyll (a/b) ratio was increased. Atrazine applied at 50 mg/kg significantly suppressed antioxidant gene expressions to the lowest. The APX gene showed overall low response to the atrazine treatments. The chloroplastic psbA gene showed highest expression with 10 mg/kg atrazine, whereas atrazine at 50 mg/kg significantly suppressed the gene expression to its lowest. Pearl millet was able to suppress oxidative stress under low atrazine levels, but high atrazine concentration could induce more oxidative damage. 相似文献