全文获取类型
收费全文 | 2843篇 |
免费 | 145篇 |
出版年
2023年 | 14篇 |
2022年 | 38篇 |
2021年 | 74篇 |
2020年 | 48篇 |
2019年 | 43篇 |
2018年 | 65篇 |
2017年 | 61篇 |
2016年 | 74篇 |
2015年 | 76篇 |
2014年 | 128篇 |
2013年 | 159篇 |
2012年 | 215篇 |
2011年 | 179篇 |
2010年 | 117篇 |
2009年 | 111篇 |
2008年 | 143篇 |
2007年 | 137篇 |
2006年 | 105篇 |
2005年 | 104篇 |
2004年 | 93篇 |
2003年 | 79篇 |
2002年 | 86篇 |
2001年 | 74篇 |
2000年 | 75篇 |
1999年 | 54篇 |
1998年 | 20篇 |
1997年 | 16篇 |
1996年 | 33篇 |
1995年 | 18篇 |
1994年 | 18篇 |
1993年 | 18篇 |
1992年 | 48篇 |
1991年 | 33篇 |
1990年 | 26篇 |
1989年 | 33篇 |
1988年 | 25篇 |
1987年 | 28篇 |
1986年 | 18篇 |
1985年 | 31篇 |
1984年 | 25篇 |
1982年 | 14篇 |
1981年 | 17篇 |
1980年 | 22篇 |
1979年 | 26篇 |
1978年 | 27篇 |
1977年 | 17篇 |
1975年 | 12篇 |
1974年 | 13篇 |
1973年 | 17篇 |
1972年 | 13篇 |
排序方式: 共有2988条查询结果,搜索用时 468 毫秒
111.
Patil Saurabh Gupta Kritika Pandit Ashish Desai Bhushan Gschliesser Siegfried Dandekar Prajakta Jain Ratnesh 《International journal of peptide research and therapeutics》2021,27(4):2831-2844
International Journal of Peptide Research and Therapeutics - The development of peptide-based formulations presents numerous challenges to the formulator due to their complexity, delicate structure... 相似文献
112.
Cluster Computing - Ever since the internet became part of the everyday lives of humans providing network security has been considered of utmost importance. Over the years lot of time and energy... 相似文献
113.
114.
C. George Priya Doss B. Rajith R. Rajasekaran Jain Srajan N. Nagasundaram C. Debajyoti 《Cell biochemistry and biophysics》2013,67(3):1307-1318
Polymorphisms in the human prion proteins lead to amino acid substitutions by the conversion of PrPC to PrPSc and amyloid formation, resulting in prion diseases such as familial Creutzfeldt–Jakob disease, Gerstmann–Straussler–Scheinker disease and fatal familial insomnia. Cation–π interaction is a non-covalent binding force that plays a significant role in protein stability. Here, we employ a novel approach by combining various in silico tools along with molecular dynamics simulation to provide structural and functional insight into the effect of mutation on the stability and activity of mutant prion proteins. We have investigated impressions of prevalent mutations including 1E1S, 1E1P, 1E1U, 1E1P, 1FKC and 2K1D on the human prion proteins and compared them with wild type. Structural analyses of the models were performed with the aid of molecular dynamics simulation methods. According to our results, frequently occurred mutations were observed in conserved sequences of human prion proteins and the most fluctuation values appear in the 2K1D mutant model at around helix 4 with residues ranging from 190 to 194. Our observations in this study could help to further understand the structural stability of prion proteins. 相似文献
115.
Pradyumna K. Mishra Gorantla V. Raghuram Hariom Panwar Deepika Jain Hemant Pandey Kewal K. Maudar 《Free radical research》2013,47(8):718-728
The role of oxidative stress is often attributed in environmental renal diseases. Isocyanates, a ubiquitous chemical group with diverse industrial applications, are known to undergo bio-transformation reactions upon accidental and occupational exposure. This study delineates the role of isocyanate-mediated mitochondrial oxidative stress in eliciting chromosomal instability in cultured human kidney epithelial cells. Cells treated with 0.005 µM concentration of methyl isocyanate displayed morphological transformation and stress-induced senescence. Along the time course, an increase in DCF fluorescence indicative of oxidative stress, depletion of superoxide dismutase (SOD) and glutathione reductase (GR) and consistent accumulation of 8-oxo-dG were noticed. Thus, endogenous oxidative stress resulted in aberrant expression of p53, p21, cyclin E and CDK2 proteins, suggestive of deregulated cell cycle, chromosomal aberrations, centromeric amplification, aneuploidy and genomic instability. 相似文献
116.
Abhinav Shrivastava M.Sc. Abdul Arif Khan Archana Shrivastav Sudhir K. Jain Pradeep K. Singhal 《Preparative biochemistry & biotechnology》2013,43(6):574-581
L-Asparaginase is an enzyme used in the treatment of acute lymphoblastic leukemia and other related malignancies. Its further use includes reduction of asparagine concentration in food products, which may lead to formation of acrylamide. Currently bacterial asparaginase is produced at industrial scale, but the enzyme isolated from bacterial origin is often associated with adverse reactions. These side effects require development of asparaginase from alternative sources. In the present study, Penicillium digitatum was explored for the production of extracellular L-asparaginase using modified Czapek–Dox media. The enzyme was purified about 60.95-fold and then kinetic study showed that the Km value of the enzyme was 1 × 10?5 M. The optimum pH and temperature for the enzyme were 7.0 and 30°C, respectively. The optimum incubation period for L-asparaginase was 15 min. This work concludes that this enzyme can be a suitable candidate due to its strong kinetic properties, and further research can usher into development of asparaginase formulation from fungal origin with less adverse effects. 相似文献
117.
Jinender Jain Anil Kumar Davender Singh 《Preparative biochemistry & biotechnology》2013,43(8):718-724
AbstractA novel protease-resistant and thermostable phytase from Bacillus subtilis subsp. subtilis JJBS250 was purified 36-fold to homogeneity with a combination of ammonium sulfate precipitation followed by Q-Sepharose and Sephadex G-50 chromatographic techniques. The estimated molecular mass of the purified phytase was 46?kDa by electrophoresis with optimal activity at pH 7.0 and 70?°C. About 19% of original activity was maintained at 80?°C for 10?min. Phytase activity was stimulated in presence of surfactants like Tween-20, Tween-80, and Triton X-100 and metal ions like Ca+2, K+, and Co+2 and it was inhibited by SDS and Mg+2, Al+2, and Fe+2. Purified enzyme showed specificity to different salts of phytic acid and values of Km and Vmax were 0.293?mM and 11.49 nmoles s?1, respectively for sodium phytate. The purified enzyme was resistant to proteases (trypsin and pepsin) that resulted in amelioration of food nutrition with simultaneous release of inorganic phosphate, reducing sugars, and soluble protein. 相似文献
118.
Jenish R Patel Ankur Jain Yi‐ying Chou Alina Baum Taekjip Ha Adolfo García‐Sastre 《EMBO reports》2013,14(9):780-787
The cytosolic pathogen sensor RIG‐I is activated by RNAs with exposed 5′‐triphosphate (5′‐ppp) and terminal double‐stranded structures, such as those that are generated during viral infection. RIG‐I has been shown to translocate on dsRNA in an ATP‐dependent manner. However, the precise role of the ATPase activity in RIG‐I activation remains unclear. Using in vitro‐transcribed Sendai virus defective interfering RNA as a model ligand, we show that RIG‐I oligomerizes on 5′‐ppp dsRNA in an ATP hydrolysis‐dependent and dsRNA length‐dependent manner, which correlates with the strength of type‐I interferon (IFN‐I) activation. These results establish a clear role for the ligand‐induced ATPase activity of RIG‐I in the stimulation of the IFN response. 相似文献
119.
John T. Bernert Sydney M. Gordon Ram B. Jain Marielle C. Brinkman Connie S. Sosnoff Tiffany H. Seyler 《Biomarkers》2013,18(2):82-93
National surveys of the exposure of non-smokers to secondhand smoke based on serum cotinine analyses have consistently identified certain groups within the population including children, males and non-Hispanic Blacks as having relatively greater exposure. Although these differences in mean serum cotinine concentrations probably represent differences in exposure of individuals in their daily lives, it is also possible that metabolic or other differences in response might influence the results. To better define the nature of those findings, we have examined the response of 40 non-smokers including both men and women and African-Americans and whites to sidestream (SS) cigarette smoke generated by a smoking machine under controlled conditions. In this study, participants were exposed to aged, diluted SS smoke (ADSS) generated in an environmental chamber with a mean air nicotine concentration of 140 μg m?3 and 8.6?ppm CO for 4?h. Salivary cotinine was measured every 30?min, and serum cotinine samples were taken prior to, and 2?h after exposure. Urinary nicotine metabolites and NNAL, a tobacco-specific nitrosamine, and 4-aminobiphenyl (4-AB) haemoglobin adducts were also measured prior to and 2?h following the exposure. Under these uniform, controlled conditions, we found a similar response to ADSS smoke exposure among all the participants. In all cases a significant increase in biomarker concentration was noted following exposure, and the short-term increases in salivary cotinine concentration were quite similar at approximately 12?pg ml?1 min?1 among the groups. In this small study, no significant differences by gender or race were seen in the mean increases observed in cotinine, NNAL or 4-AB adducts following 4?h of exposure. Thus, our results are most consistent with a relatively uniform response in tobacco biomarker concentrations following short-term exposure to ADSS tobacco smoke, and suggest that biomarker measurements are capable of effectively indicating increases in exposure among groups of non-smokers. 相似文献
120.
AbstractThe glutathione S-transferase (GSTs) are polymorphic supergene family of detoxification enzymes that are involved in the metabolism of numerous potential carcinogens. Several allelic variants of polymorphic GSTs show impaired enzyme activity and are suspected to increase the susceptibility to various cancers. To find out the association of GST variants with risk of gallbladder cancer, the distribution of polymorphisms in the GST family of genes (GSTT1, GSTM1, GSTP1, and GSTM3) were studied in 106 cancer patients and 201 healthy controls. Genotypes were analysed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP). The frequencies of GSTM1 null and GSTM3*BB genotypes did not differ between patients and controls. The overall frequency of GSTT1 null was lower in cases as compared with controls (p=0.003, Odds ratio (OR)?=?0.2, 95% confidence interval (CI), 0.1–0.6). After sex stratification, the GSTT1 null frequency was reduced only in female patients (p=0.008, OR?=?0.2, 95% CI?=?0.1–0.6). However, the GSTP1, ile/val genotype and the val allele were significantly higher in cases than controls (p=0.013, OR?=?1.9, 95% CI?=?1.1–3.1; p=0.027, OR?=?1.5, 95% CI?=?1.0–2.1), respectively. To study gene–gene interactions, a combined risk of gallbladder cancer due to ile/val or val/val were calculated in combination with null alleles of GSTM1 and GSTT1 or the *B allele of GSTM3, but there was no enhancement of risk. Gallstones were present in 57.5% of patients with gallbladder cancer, but there were no significant differences between allelic/genotype frequencies of the studied GST genes polymorphisms between patients with or without gallstones. To best of our knowledge, this is the first paper showing ile/val genotypes and val allele of GSTP1 to be associated with higher risk of gallbladder cancer. 相似文献