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   472549篇
  免费   50825篇
  国内免费   467篇
  2018年   4951篇
  2017年   4714篇
  2016年   6693篇
  2015年   9525篇
  2014年   10995篇
  2013年   14767篇
  2012年   17400篇
  2011年   17652篇
  2010年   11647篇
  2009年   10380篇
  2008年   15244篇
  2007年   15696篇
  2006年   14789篇
  2005年   13920篇
  2004年   13995篇
  2003年   13010篇
  2002年   12599篇
  2001年   19487篇
  2000年   19394篇
  1999年   15429篇
  1998年   5598篇
  1997年   5553篇
  1996年   5280篇
  1995年   5284篇
  1994年   4947篇
  1993年   4948篇
  1992年   12750篇
  1991年   12668篇
  1990年   12417篇
  1989年   11876篇
  1988年   11022篇
  1987年   10390篇
  1986年   9907篇
  1985年   9685篇
  1984年   8027篇
  1983年   6956篇
  1982年   5246篇
  1981年   4725篇
  1980年   4391篇
  1979年   7523篇
  1978年   6065篇
  1977年   5382篇
  1976年   5057篇
  1975年   5869篇
  1974年   6436篇
  1973年   6231篇
  1972年   5579篇
  1971年   5182篇
  1970年   4390篇
  1969年   4320篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Connecdenn 1/2 are DENN (differentially expressed in normal and neoplastic cells) domain-bearing proteins that function as GEFs (guanine nucleotide exchange factors) for the small GTPase Rab35. Disruption of connecdenn/Rab35 function leads to defects in the recycling of multiple cargo proteins from endosomes with altered cell function, yet the regulation of connecdenn GEF activity is unexplored. We now demonstrate that connecdenn 1/2 are autoinhibited such that the purified, full-length proteins have significantly less Rab35 binding and GEF activity than the isolated DENN domain. Both proteins are phosphorylated with prominent phosphorylation sites between residues 500 and 600 of connecdenn 1. A large scale proteomics screen revealed that connecdenn 1 is phosphorylated at residues Ser-536 and Ser-538 in an Akt-dependent manner in response to insulin stimulation of adipocytes. Interestingly, we find that an Akt inhibitor reduces connecdenn 1 interaction with Rab35 after insulin treatment of adipocytes. Remarkably, a peptide flanking Ser-536/Ser-538 binds the DENN domain of connecdenn 1, whereas a phosphomimetic peptide does not. Moreover, connecdenn 1 interacts with 14-3-3 proteins, and this interaction is also disrupted by Akt inhibition and by mutation of Ser-536/Ser-538. We propose that Akt phosphorylation of connecdenn 1 downstream of insulin activation regulates connecdenn 1 function through an intramolecular interaction.  相似文献   
2.
There is a diverse range of microbiological challenges facing the food, healthcare and clinical sectors. The increasing and pervasive resistance to broad‐spectrum antibiotics and health‐related concerns with many biocidal agents drives research for novel and complementary antimicrobial approaches. Biofilms display increased mechanical and antimicrobial stability and are the subject of extensive research. Cold plasmas (CP) have rapidly evolved as a technology for microbial decontamination, wound healing and cancer treatment, owing to the chemical and bio‐active radicals generated known collectively as reactive oxygen and nitrogen species. This review outlines the basics of CP technology and discusses the interactions with a range of microbiological targets. Advances in mechanistic insights are presented and applications to food and clinical issues are discussed. The possibility of tailoring CP to control specific microbiological challenges is apparent. This review focuses on microbiological issues in relation to food‐ and healthcare‐associated human infections, the role of CP in their elimination and the current status of plasma mechanisms of action.  相似文献   
3.
4.
The application of pectinases in industrial olive-oil processes is restricted by its production cost. Consequently, new fungal strains able to produce higher pectinase titers are required. The aim of this work was to study the capability of Aspergillus giganteus NRRL10 to produce pectinolytic enzymes by SSF and evaluate the application of these in olive-oil extraction. A. giganteus was selected among 12 strains on the basis of high pectinolytic activity and stability. A mixture composed by wheat bran, orange, and lemon peels was selected as the best substrate for enzyme production. Statistical analyses of the experimental design indicated that pH, temperature, and CaCl2 are the main factors that affect the production. Subsequently, different aeration flows were tested in a tray reactor; the highest activity was achieved at 20 L min?1 per kilogram of dry substrate (kgds). Finally, the pectinolytic enzymes from A. giganteus improved the oil yield and rheological characteristics without affecting oil chemical properties.  相似文献   
5.
6.
The effect of exercise-induced oxidative stress on health and aging is not clearly explained. This study examined the effects of habitual sport practice, age, and submaximal exercise on the blood markers of oxidative stress, muscle damage, and antioxidant response. Seventy-two healthy men were grouped by their habitual sport practice: inactive (<1.5 h/week), recreational (3–8 h/week), and trained athletes (>8 h/week), and further divided by age: young (18–25 years), adult (40–55 years), and senior (>55 years). Blood samples were collected at rest and after submaximal effort. Hydroperoxides and superoxide dismutase, glutathione peroxidase, and catalase activities were measured by spectrophotometry. Nuclear DNA damage was analyzed by comet assay. The alpha-actin release was analyzed by Western blot. Alpha-tocopherol, retinol, and coenzyme-Q10 were quantified by high-performance liquid chromatography analysis. Data was analyzed through a factorial ANOVA and the Bonferroni post hoc test. Lipid peroxidation increased significantly with age and submaximal effort (p?<?0.05). However, the trained athlete group presented lower lipid peroxidation compared with the recreational group (MD?=?2.079, SED?=?0.58, p?=?0.002) and inactive group (MD?=?1.979, SED?=?0.61, p?=?0.005). Trained athletes showed significant higher alpha-actin levels (p?<?0.001) than the other groups. Recreational group showed lower nuclear DNA damage than trained athletes (MD?=?3.681, SED?=?1.28, p?=?0.015). Nevertheless, the inactive group presented significantly higher superoxide dismutase and catalase (p?<?0.05) than the other groups. Data suggested that habitual competitive training practice could prevent age-related increases of plasma lipid peroxidation, which, according with our results, cannot be entirely attributed to blood antioxidant defense systems.  相似文献   
7.
Introduction: B cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy considered as the most common leukemia in the Western world. The understanding of B cell differentiation is crucial for the diagnosis, prognosis, and treatment of the disease.

Areas covered: In this review, B-cell ontogeny and its relation with the CLL development, in combination with the proteomic approaches which could provide a deep characterization of the disease through the characterization of the cellular signaling pathways involved in the pathological cells is described.

Expert commentary: Although conventional strategies (genome sequencing, morphology assays, and immunophenotyping by flow cytometry and/or immunochemistry) have allowed the establishment of the disease stage based on different parameters, it is still necessary to utilize novel approaches (e.g., proteomics) that have the potential to simultaneously analyze thousands of molecules to improve understanding of CLL.  相似文献   

8.
Identifying which introduced species have the greatest potential for establishment, spread and impact is critical for prioritizing pre‐ and post‐border control. Using species distribution modelling and existing species locations we assessed the establishment risk based on the climatic suitability areas of 25 plant species listed as eradication targets under South African regulations. To improve confidence, three bioclimatic models were used to predict the potential distribution of each species. This information was combined with the number of localities and the “eradication feasibility syndromes” in a scoring‐categorical system to rank the species. Three management groups were identified. Group “A” includes species with medium‐high establishment risk and higher likelihood to be eradicated, these species should be a priority for eradication. Group “B” includes species with a medium‐low establishment risk but given the low number of known population and the species characteristics, eradication is likely to be feasible. Finally species in group “C” scored a medium‐high establishment risk but the eradication would be difficult due to the high number of known localities. This ranking provides a rapid method to prioritize the management towards the eradication of new potential invasive plant species in the country combining the establishment risk, known number of localities and the inferred eradication success.  相似文献   
9.
The study of the evolutionary interrelationships among the species encompassed in the Neotropical genus Argia (Zygoptera: Coenagrionidae) has been neglected. The goal of this study is to infer the phylogenetic relationships among 36 species of Argia Rambur, 1842, using complementary data sets (i.e., larval morphology and mitochondrial DNA). The morphological data set comprises 76% of the larvae currently described for this genus and includes 97 morphological characters. From those, 47 characters have not been previously used in taxonomic studies involving dragonflies’ larvae. This is the first cladistic study based on larvae morphology for species within the suborder Zygoptera. Data partitions were analyzed individually, as well as total evidence, using parsimony and Bayesian inference as criteria for optimal-tree selection. The results support the monophyly of the North American species of Argia. This genus can be identified by the combination of eight synapomorphies, four of which are exclusively found in Argia. According to the optimal trees, the individual data sets (i.e., morphology and DNA sequences) have a high level of homoplasy, resulting in soft polytomies and low support for several nodes. The specific relationships of the terminal units differ between the phylogenies; nonetheless, there is historical congruence among them. Within Argia, five clades were consistently recovered. Most of those clades have been identified, at least in part, in previous phylogenetic and taxonomic studies. Indubitably, the morphological characters from larvae have historical signal useful for cladistic and taxonomic inference. Therefore, it should be a priority to pay more attention to this source of characters.  相似文献   
10.
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