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   496篇
  免费   15篇
  国内免费   1篇
  2023年   4篇
  2022年   9篇
  2021年   15篇
  2020年   15篇
  2019年   13篇
  2018年   12篇
  2017年   8篇
  2016年   25篇
  2015年   19篇
  2014年   18篇
  2013年   36篇
  2012年   40篇
  2011年   44篇
  2010年   11篇
  2009年   17篇
  2008年   32篇
  2007年   34篇
  2006年   32篇
  2005年   31篇
  2004年   25篇
  2003年   31篇
  2002年   13篇
  2001年   8篇
  2000年   4篇
  1999年   5篇
  1997年   1篇
  1996年   1篇
  1993年   1篇
  1991年   1篇
  1990年   1篇
  1989年   2篇
  1988年   2篇
  1987年   1篇
  1966年   1篇
排序方式: 共有512条查询结果,搜索用时 234 毫秒
141.
In this study, the potential use of the fungus Pleurotus sajor caju to remove phenols (i.e., phenol, o-chlorophenol, p-chlorophenol and 2,4,6-trichlorophenol) from aqueous solutions was evaluated. Biosorption of phenol or chlorophenols reached equilibrium in 4 h. The maximum adsorptions of phenol and chlorophenols onto the Pleurotus sajor caju were 0.95 mmol/g for phenol, 1.24 mmol/g for o-chlorophenol, 1.47 mmol/g for p-chlorophenol and 1.89 mmol/g for 2,4,6-trichlorophenol. The affinity order was as follows: 2,4,6-trichlorophenol> p-chlorophenol> o-chlorophenol>phenol. Phenol and chlorophenols bindings onto Pleurotus sajor caju were clearly pH dependent. The adsorption of phenol and chlorophenols increased with increasing pH. Desorption was achieved using methanol solution (30%, v/v). Pleurotus sajor caju biomass is suitable for reuse for more than five cycles without noticeable loss of adsorption capacity.  相似文献   
142.
143.
PKC-alpha regulates cardiac contractility and propensity toward heart failure   总被引:16,自引:0,他引:16  
The protein kinase C (PKC) family of serine/threonine kinases functions downstream of nearly all membrane-associated signal transduction pathways. Here we identify PKC-alpha as a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. Hearts of Prkca-deficient mice are hypercontractile, whereas those of transgenic mice overexpressing Prkca are hypocontractile. Adenoviral gene transfer of dominant-negative or wild-type PKC-alpha into cardiac myocytes enhances or reduces contractility, respectively. Mechanistically, modulation of PKC-alpha activity affects dephosphorylation of the sarcoplasmic reticulum Ca(2+) ATPase-2 (SERCA-2) pump inhibitory protein phospholamban (PLB), and alters sarcoplasmic reticulum Ca(2+) loading and the Ca(2+) transient. PKC-alpha directly phosphorylates protein phosphatase inhibitor-1 (I-1), altering the activity of protein phosphatase-1 (PP-1), which may account for the effects of PKC-alpha on PLB phosphorylation. Hypercontractility caused by Prkca deletion protects against heart failure induced by pressure overload, and against dilated cardiomyopathy induced by deleting the gene encoding muscle LIM protein (Csrp3). Deletion of Prkca also rescues cardiomyopathy associated with overexpression of PP-1. Thus, PKC-alpha functions as a nodal integrator of cardiac contractility by sensing intracellular Ca(2+) and signal transduction events, which can profoundly affect propensity toward heart failure.  相似文献   
144.

Background  

Cutaneous horns (cornu cutaneum) are uncommon lesions consisting of keratotic material resembling that of an animal horn. Cutaneous horn may arise from a wide range of the epidermal lesions, which may be benign, premalignant or malignant.  相似文献   
145.

Background

Tuberculosis continues to be an important health problem in the world. Besides pulmonary involvement extrapulmonary involvement becomes an affair in developing countries, even in developed countries.

Case presentation

A thirty-six year old male patient was admitted with abdominal pain, diarrhea, nausea, vomiting and fever which had started one week before. The patient had been followed up with predialisis Chronic Renal Failure(CRF) diagnosis for 4 years and receiving continuous ambulatory peritoneal dialysis (CAPD) treatment for 4 months. In peritoneal fluid, 1600/mm3 cells were detected and 70% of them were polymorphonuclear leukocytosis. The patient begun nonspesific antibiotherapy but no benefit was obtained after 12 days and peritoneal fluid bacterial cultures remained negative. Peritoneal smear was positive for Asid-fast basilli (AFB), and antituberculosis therapy was started with isoniazid, rifampicine, ethambutol and pyrazinamide. After 15 days his peritoneal fluid cell count was decreased and his symptoms were relieved. Peritoneal fluid tuberculosis culture was found positive.

Conclusion

Considering this case, we think that in patients with CAPD catheter and peritonitis; when peritoneal fluid leukocytes are high and PMNL are dominant, AFB and tuberculosis culture must be investigated besides bacterial culture routinely.  相似文献   
146.
The storage of renewable electrical energy within chemical bonds of biofuels and other chemicals is a route to decreasing petroleum usage. A critical challenge is the efficient transfer of electrons into a biological host that can covert this energy into high energy organic compounds. In this paper, we describe an approach whereby biomass is grown using energy obtained from a soluble mediator that is regenerated electrochemically. The net result is a separate-stage reverse microbial fuel cell (rMFC) that fixes CO2 into biomass using electrical energy. We selected ammonia as a low cost, abundant, safe, and soluble redox mediator that facilitated energy transfer to biomass. Nitrosomonas europaea, a chemolithoautotroph, was used as the biocatalyst due to its inherent capability to utilize ammonia as its sole energy source for growth. An electrochemical reactor was designed for the regeneration of ammonia from nitrite, and current efficiencies of 100% were achieved. Calculations indicated that overall bioproduction efficiency could approach 2.7±0.2% under optimal electrolysis conditions. The application of chemolithoautotrophy for industrial bioproduction has been largely unexplored, and results suggest that this and related rMFC platforms may enable biofuel and related biochemical production.  相似文献   
147.
Analysis of biological processes is frequently performed with the help of phenotypic assays where data is mostly acquired in single end-point analysis. Alternative phenotypic profiling techniques are desired where time-series information is essential to the biological question, for instance to differentiate early and late regulators of cell proliferation in loss-of-function studies. So far there is no study addressing this question despite of high unmet interests, mostly due to the limitation of conventional end-point assaying technologies. We present the first human kinome screen with a real-time cell analysis system (RTCA) to capture dynamic RNAi phenotypes, employing time-resolved monitoring of cell proliferation via electrical impedance. RTCA allowed us to investigate the dynamics of phenotypes of cell proliferation instead of using conventional end-point analysis. By introducing data transformation with first-order derivative, i.e. the cell-index growth rate, we demonstrate this system suitable for high-throughput screenings (HTS). The screen validated previously identified inhibitor genes and, additionally, identified activators of cell proliferation. With the information of time kinetics available, we could establish a network of mitotic-event related genes to be among the first displaying inhibiting effects after RNAi knockdown. The time-resolved screen captured kinetics of cell proliferation caused by RNAi targeting human kinome, serving as a resource for researchers. Our work establishes RTCA technology as a novel robust tool with biological and pharmacological relevance amenable for high-throughput screening.  相似文献   
148.
BackgroundBreast cancer patients who are resistant to neoadjuvant chemotherapy (NeoCT) have a poor prognosis. There is a pressing need to develop in vivo models of chemo resistant tumors to test novel therapeutics. We hypothesized that patient-derived breast cancer xenografts (BCXs) from chemo- naïve and chemotherapy-exposed tumors can provide high fidelity in vivo models for chemoresistant breast cancers.MethodsPatient tumors and BCXs were characterized with short tandem repeat DNA fingerprinting, reverse phase protein arrays, molecular inversion probe arrays, and next generation sequencing.ResultsForty-eight breast cancers (24 post-chemotherapy, 24 chemo-naïve) were implanted and 13 BCXs were established (27%). BCX engraftment was higher in TNBC compared to hormone-receptor positive cancer (53.8% vs. 15.6%, p = 0.02), in tumors from patients who received NeoCT (41.7% vs. 8.3%, p = 0.02), and in patients who had progressive disease on NeoCT (85.7% vs. 29.4%, p = 0.02). Twelve patients developed metastases after surgery; in five, BCXs developed before distant relapse. Patients whose tumors developed BCXs had a lower recurrence-free survival (p = 0.015) and overall survival (p<0.001). Genomic losses and gains could be detected in the BCX, and three models demonstrated a transformation to induce mouse tumors. However, overall, somatic mutation profiles including potential drivers were maintained upon implantation and serial passaging. One BCX model was cultured in vitro and re-implanted, maintaining its genomic profile.ConclusionsBCXs can be established from clinically aggressive breast cancers, especially in TNBC patients with poor response to NeoCT. Future studies will determine the potential of in vivo models for identification of genotype-phenotype correlations and individualization of treatment.  相似文献   
149.
Sleep and Biological Rhythms - Obstructive Sleep Apnea Syndrome (OSAS) is characterized by desaturation in blood oxygen level and sleep fragmentation because of repeated upper airway obstruction....  相似文献   
150.
IntroductionAutoreactive T cells are a central element in many systemic autoimmune diseases. The generation of these pathogenic T cells is instructed by antigen-presenting cells (APCs). However, signaling pathways in APCs that drive autoimmune diseases, such as rheumatoid arthritis, are not understood.MethodsWe measured phenotypic maturation, cytokine production and induction of T cell proliferation of APCs derived from wt mice and mice with a myeloid-specific deletion of PTEN (myeloid PTEN-/-) in vitro and in vivo. We induced collagen-induced arthritis (CIA) and K/BxN serum transfer arthritis in wt and myeloid-specific PTEN-/- mice. We measured the cellular composition of lymph nodes by flow cytometry and cytokines in serum and after ex vivo stimulation of T cells.ResultsWe show that myeloid-specific PTEN-/- mice are almost protected from CIA. Myeloid-specific deletion of PTEN leads to a significant reduction of cytokine expression pivotal for the induction of systemic autoimmunity such as interleukin (IL)-23 and IL-6, leading to a significant reduction of a Th17 type of immune response characterized by reduced production of IL-17 and IL-22. In contrast, myeloid-specific PTEN deficiency did not affect K/BxN serum transfer arthritis, which is independent of the adaptive immune system and solely depends on innate effector functions.ConclusionsThese data demonstrate that the presence of PTEN in myeloid cells is required for the development of CIA. Deletion of PTEN in myeloid cells inhibits the development of autoimmune arthritis by preventing the generation of a pathogenic Th17 type of immune response.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0742-y) contains supplementary material, which is available to authorized users.  相似文献   
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