首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1368篇
  免费   104篇
  国内免费   1篇
  1473篇
  2023年   13篇
  2022年   36篇
  2021年   61篇
  2020年   28篇
  2019年   52篇
  2018年   41篇
  2017年   34篇
  2016年   61篇
  2015年   64篇
  2014年   73篇
  2013年   102篇
  2012年   83篇
  2011年   91篇
  2010年   60篇
  2009年   50篇
  2008年   71篇
  2007年   62篇
  2006年   64篇
  2005年   57篇
  2004年   52篇
  2003年   53篇
  2002年   35篇
  2001年   12篇
  2000年   10篇
  1999年   25篇
  1998年   11篇
  1997年   9篇
  1996年   8篇
  1995年   9篇
  1994年   4篇
  1993年   5篇
  1992年   4篇
  1991年   11篇
  1990年   11篇
  1989年   6篇
  1988年   8篇
  1987年   13篇
  1986年   9篇
  1985年   4篇
  1984年   7篇
  1982年   4篇
  1980年   4篇
  1979年   6篇
  1978年   6篇
  1977年   4篇
  1976年   7篇
  1975年   3篇
  1974年   7篇
  1973年   5篇
  1972年   5篇
排序方式: 共有1473条查询结果,搜索用时 15 毫秒
961.
Antibiotic-resistant Staphylococci are a global issue affecting humans, animals, and numerous natural environments. Antibiotic-resistant Staphylococcus epidermidis is an opportunistic pathogen frequently isolated from patients and healthy individuals. This study aimed to examine the antibiotic resistance of S. epidermidis isolated from patients, healthy students and compare the results with antibiotic-resistant bacteria isolated from pasteurized milk. Clinical strain isolation was performed in several hospitals in the Riyadh. Skin swabs from 100 healthy undergraduate candidate students were obtained at King Saud University. The pasteurized milk samples were obtained from local market (company, X). After isolation, identification and susceptibility tests were performed using an automated system. A multiplex tuf gene-based PCR assay was used to confirm identification. Biofilm production and biofilm-related gene expression were studied. S. epidermidis represented 17% of clinical bacterial isolates, and 1.7% of isolates obtained from healthy students were multiantibiotic-resistant. All patient strains were teicoplanin- and vancomycin-susceptible, while all student strains were gentamicin-, levofloxacin-, moxifloxacin-, and trimethoprim/sulfamethoxazole-susceptible. All the bacteria isolated from pasteurized milk were benzylpenicillin and oxacillin-resistant strains. Of the S. epidermidis strains, 91% could produce biofilms, and mecA, icaADBR, ica-ADB, ica-AD, ica-A only, and ica-C only were expressed in 83, 17.1, 25.7, 37.1, 20, and 0% of the strains, respectively. This work demonstrates that S. epidermidis can be accurately identified using a multiplex tuf-based assay, and that multiantibiotic-resistant S. epidermidis strains are widespread amongst patients and healthy students.  相似文献   
962.
ObjectivePhosphate (P) and zinc (Zn) are essential plant nutrients required for nodulation, nitrogen-fixation, plant growth and yield. Mostly applied P and Zn nutrients in the soil are converted into unavailable form. A small number of soil microbes have the ability to transform unsolvable forms of P and Zn to an available form. P-Zn-solubilizing rhizobacteria are potential alternates for P and Zn supplement. In the present study, the effect of two P-Zn-solubilizing bacterial strains (Bacillus sp. strain AZ17 and Pseudomonas sp. strain AZ5) was evaluated on the growth of chickpea plant.MethodologyBoth strains were purified from the rhizospheric soil of chickpea plant grown-up in sandy soil and rain-fed area (Thal desert). In vitro, both strains solubilize P and Zn as well both strain produce IAA and organic acids. In the field experiments, conducted in the rain-fed area, the positive influence of inoculation with both bacterial isolates AZ5 and AZ17 on chickpea growth was observed.ResultsThe application of inoculum (strains AZ5 and AZ17) resulted in up to 17.47% and 17.34% increase in grain yield of both types of chickpea grown in fertilized and non-fertilized soil, respectively over non-inoculated control. Strain AZ5 was the most effective inoculum, increasing up to 17.47%, 16.04%, 26.32%, 22.53%, 26.12% and 22.59% in grain yield, straw weight, nodules number, dry weight of nodules, Zn uptake and P uptake respectively, over control.ConclusionThese results indicated that Pseudomonas sp. strain AZ5 and Bacillus sp. strain AZ17 can serve as effective microbial inocula for chickpea, particularly in the rain-fed area.  相似文献   
963.

Objective

To study the putative effects of Advanced Oxidation Protein Products (AOPPs) and Advanced Glycation End Products (AGEs) in the development and progression of cardiovascular disease (CVD).

Methodology

AGEs, AOPPs, e-NOS, lipid profile, circulating stress and inflammatory biomarkers were evaluated among fifty cardiovascular patients and fifty controls. Independent student’s t-test was done for statistical analysis.

Results

The malondialdehyde mean level in CVD patients (5.45?nmol/ml) was significantly higher than control (1.36?nmol/ml) (p value?=?0.018). Nitric oxide in CVD patients (55.72?ng/ml) was remarkably increased as compared to normal subjects (19.19?ng/ml). A significant change in the mean serum level of AGEs in CVD patients (2.74?ng/ml) and normal individuals (0.85?ng/ml) was recorded (p value?=?0.000). The AOPPs also showed significant increased levels in CVD group (132.07?ng/ml) in comparison with normal subjects (83.05?ng/ml) (p value?=?0.011). The mean eNOS serum level in CVD group (15.50?U/L) was higher than control group (11.28?U/L) (p value?=?0.004). Cardiovascular disease patients, in comparison with healthy controls, showed increased level of total cholesterol (5.48?mmol/L vs 4.45?mmol/L), triglycerides (2.59?mmol/L vs 1.24?mmol/L), and low density lipoprotein (2.47?mmol/L vs 2.31?mmol/L) along with decrease in high density lipoprotein (1.39?mmol/L vs 1.74?mmol/L). The mean MMP-11 serum levels in CVD group (98.69?ng/ml) was almost double of control group (45.60?ng/ml) (p value?=?0.017). The mean serum level of TNF-α and IL1-α were 32.16?pg/ml and 6.64?pg/ml in CVD patient. The significant decreasing trend of SOD (p value?=?0.041), CAT (p value?=?0.018), GSH (p value?=?0.036) and GRx (p value?=?0.029) but increasing drift of GPx (0.023) level was observed in CVD patients.

Conclusion

This study provides strong evidence that CVD patients presented with elevated oxidative stress, enhanced inflammation and lipid profile in their serum. Therefore, the study strongly approves that AGEs, AOPPs, inflammatory and lipoxidative biomarkers hold predictive potential in causing and aggravating the disease, thus by controlling these factors CVD progression can be inhibited.  相似文献   
964.
965.
InhA (Enoyl-ACP reductase) plays a crucial role in the biosynthetic pathway of cell wall synthesis in Mycobacterium tuberculosis (Mtb). Isoniazid (INH) is an important first-line drug, which inhibits InhA. The rapid increase in resistance to INH and currently marketed drugs as well as emergence of MDR-TB and XDR-TB has complicated the diagnosis and treatment of Mtb with ever increasing threat to human kind. Herein, we report novel N-methyl carbazole derivatives as potential anti-TB compounds acting directly via InhA inhibition. All the synthesized final compounds were screened against Mtb virulent cell line H37Rv and investigated the InhA enzyme inhibition. Interestingly, compound 9e displayed promising inhibition (91%) at 50 µM concentration and IC50 of 2.82 µM against InhA. To understand the ligand receptor interaction between compound 9e and InhA, molecular docking and molecular dynamics experiments were performed. The computational results were in agreement with the observed experimental data. Further, the cytotoxicity studies on mammalian cells revealed that all the compounds were safe.  相似文献   
966.
Neuropathic pain is a debilitating form of treatment-resistant chronic pain caused by damage to the nervous system. Cannabinoids have been known for suppressing neuropathic pain by modulating the endo cannabinoid system. Since the canonical Wnt/β-catenin signaling has recently been implicated in pain sensation, we investigated the impact of major cannabinoids (16) from the leaves of Cannabis sativa and an epoxy derivative of compound 2, here upon referred to as 2a, on modulating Wnt/β-catenin signaling pathway. The results presented in this study show that compound 1, 2 and 2a exhibited potent inhibitory activity against Wnt/β-catenin pathway in a dose-dependent manner. Compound 2a was seen to inhibit this pathway at slightly lower concentrations than its parent molecule 2, under similar conditions. Taken together, compound 1, 2 and 2a, by virtue of their inhibition of Wnt-catenin signaling pathway, could be developed as effective neuroprotective agents for the management of neuropathic pain.  相似文献   
967.
Cicer arietinum (chickpea) is a legume very sensitive to salinity, and so are most of its rhizobial symbionts belonging to the species Mesorhizobium ciceri. We observed that exogenous trehalose (i.e., added to the growth medium) can significantly improve growth of M. ciceri strain Rch125 under moderate salinity. In order to test if endogenous trehalose (i.e., synthesized by the cell) could also enhance salt tolerance, strain Rch125 was genetically modified with various trehalose biosynthesis genes from Sinorhizobium meliloti 1021 (otsA, treS, treY) and Mesorhizobium loti MAFF 303099 (otsAB). We found that overexpression of otsA or otsAB, but not treS or treY, significantly improved M. ciceri Rch125 growth in saline media. This growth improvement correlated with enhanced trehalose accumulation in otsA- and otsAB-modified cells, suggesting that increased trehalose synthesis via trehalose-6-phosphate can enhance bacterial salt tolerance. Chickpea plants inoculated with M. ciceri Rch125 derivatives carrying extra otsAB or otsA genes formed more nodules and accumulated more shoot biomass than wild type inoculated plants when grown in the presence of NaCl. These results support the notion that improved salt tolerance of the bacterial symbiont can alleviate the negative effects of salinity on chickpeas, and that such improvement in M. ciceri can be achieved by manipulating trehalose metabolism.  相似文献   
968.
969.
Thoracic X-ray therapy (XRT), used in cancer treatment, is associated with increased risk of heart failure. XRT-mediated injury to the heart induces an inflammatory response leading to cardiomyopathy. The aim of this study was to determine the role of interleukin (IL)-1 in response to XRT injury to the heart and on the cardiomyopathy development in the mouse. Female mice with genetic deletion of the IL-1 receptor type I (IL-1R1 knockout mice [IL-1R1 KO]) and treatment with recombinant human IL-1 receptor antagonist anakinra, 10 mg/kg twice daily for 7 d, were used as independent approaches to determine the role of IL-1. Wild-type (wt) or IL-1R1 KO mice were treated with a single session of XRT (20 or 14 gray [Gy]). Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson’s trichrome was used to assess myocardial fibrosis and pericardial thickening. After 20 Gy, the contractile reserve was impaired in wt mice at d 3, and the LV ejection fraction (EF) was reduced after 4 months when compared with sham-XRT. IL-1R1 KO mice had preserved contractile reserve at 3 d and 4 months and LVEF at 4 months after XRT. Anakinra treatment for 1 d before and 7 d after XRT prevented the impairment in contractile reserve. A significant increase in LV end-diastolic pressure, associated with increased myocardial interstitial fibrosis and pericardial thickening, was observed in wt mice, as well as in IL-1R1 KO–or anakinra-treated mice. In conclusion, induction of IL-1 by XRT mediates the development of some, such as the contractile impairment, but not all aspects of the XRT-induced cardiomyopathy, such as myocardial fibrosis or pericardial thickening.  相似文献   
970.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号