全文获取类型
收费全文 | 2416篇 |
免费 | 183篇 |
国内免费 | 4篇 |
出版年
2023年 | 12篇 |
2022年 | 46篇 |
2021年 | 84篇 |
2020年 | 32篇 |
2019年 | 57篇 |
2018年 | 50篇 |
2017年 | 38篇 |
2016年 | 71篇 |
2015年 | 128篇 |
2014年 | 106篇 |
2013年 | 155篇 |
2012年 | 170篇 |
2011年 | 150篇 |
2010年 | 93篇 |
2009年 | 75篇 |
2008年 | 119篇 |
2007年 | 115篇 |
2006年 | 108篇 |
2005年 | 99篇 |
2004年 | 92篇 |
2003年 | 84篇 |
2002年 | 87篇 |
2001年 | 29篇 |
2000年 | 27篇 |
1999年 | 18篇 |
1998年 | 36篇 |
1997年 | 14篇 |
1996年 | 17篇 |
1995年 | 22篇 |
1992年 | 13篇 |
1991年 | 18篇 |
1990年 | 20篇 |
1989年 | 19篇 |
1988年 | 12篇 |
1987年 | 15篇 |
1985年 | 15篇 |
1984年 | 12篇 |
1983年 | 17篇 |
1982年 | 30篇 |
1981年 | 26篇 |
1980年 | 16篇 |
1977年 | 13篇 |
1976年 | 11篇 |
1975年 | 12篇 |
1974年 | 15篇 |
1973年 | 15篇 |
1970年 | 14篇 |
1969年 | 15篇 |
1968年 | 10篇 |
1967年 | 10篇 |
排序方式: 共有2603条查询结果,搜索用时 140 毫秒
891.
892.
893.
Kurt H. Piepenbrink Grace A. Maldarelli Claudia F. Martinez de la Pe?a George L. Mulvey Greg A. Snyder Leon De Masi Erik C. von Rosenvinge Sebastian Günther Glen D. Armstrong Michael S. Donnenberg Eric J. Sundberg 《The Journal of biological chemistry》2014,289(7):4334-4345
Type IV pili are produced by many pathogenic Gram-negative bacteria and are important for processes as diverse as twitching motility, cellular adhesion, and colonization. Recently, there has been an increased appreciation of the ability of Gram-positive species, including Clostridium difficile, to produce Type IV pili. Here we report the first three-dimensional structure of a Gram-positive Type IV pilin, PilJ, demonstrate its incorporation into Type IV pili, and offer insights into how the Type IV pili of C. difficile may assemble and function. PilJ has several unique structural features, including a dual-pilin fold and the incorporation of a structural zinc ion. We show that PilJ is incorporated into Type IV pili in C. difficile and present a model in which the incorporation of PilJ into pili exposes the C-terminal domain of PilJ to create a novel interaction surface. 相似文献
894.
Lindsay Murdock Tangi Burke Chelsea Coumoundouros Doreen E. Culham Charles E. Deutch James Ellinger Craig H. Kerr Samantha M. Plater Eric To Geordie Wright Janet M. Wood 《Applied and environmental microbiology》2014,80(17):5366-5378
Osmolyte accumulation and release can protect cells from abiotic stresses. In Escherichia coli, known mechanisms mediate osmotic stress-induced accumulation of K+ glutamate, trehalose, or zwitterions like glycine betaine. Previous observations suggested that additional osmolyte accumulation mechanisms (OAMs) exist and their impacts may be abiotic stress specific. Derivatives of the uropathogenic strain CFT073 and the laboratory strain MG1655 lacking known OAMs were created. CFT073 grew without osmoprotectants in minimal medium with up to 0.9 M NaCl. CFT073 and its OAM-deficient derivative grew equally well in high- and low-osmolality urine pools. Urine-grown bacteria did not accumulate large amounts of known or novel osmolytes. Thus, CFT073 showed unusual osmotolerance and did not require osmolyte accumulation to grow in urine. Yeast extract and brain heart infusion stimulated growth of the OAM-deficient MG1655 derivative at high salinity. Neither known nor putative osmoprotectants did so. Glutamate and glutamine accumulated after growth with either organic mixture, and no novel osmolytes were detected. MG1655 derivatives retaining individual OAMs were created. Their abilities to mediate osmoprotection were compared at 15°C, 37°C without or with urea, and 42°C. Stress protection was not OAM specific, and variations in osmoprotectant effectiveness were similar under all conditions. Glycine betaine and dimethylsulfoniopropionate (DMSP) were the most effective. Trimethylamine-N-oxide (TMAO) was a weak osmoprotectant and a particularly effective urea protectant. The effectiveness of glycine betaine, TMAO, and proline as osmoprotectants correlated with their preferential exclusion from protein surfaces, not with their propensity to prevent protein denaturation. Thus, their effectiveness as stress protectants correlated with their ability to rehydrate the cytoplasm. 相似文献
895.
Sabrina L. Mitchell Robert Goodloe Kristin Brown-Gentry Sarah A. Pendergrass Deborah G. Murdock Dana C. Crawford 《Human genetics》2014,133(7):861-868
Mitochondrial DNA (mtDNA) haplogroups are valuable for investigations in forensic science, molecular anthropology, and human genetics. In this study, we developed a custom panel of 61 mtDNA markers for high-throughput classification of European, African, and Native American/Asian mitochondrial haplogroup lineages. Using these mtDNA markers, we constructed a mitochondrial haplogroup classification tree and classified 18,832 participants from the National Health and Nutrition Examination Surveys (NHANES). To our knowledge, this is the largest study to date characterizing mitochondrial haplogroups in a population-based sample from the United States, and the first study characterizing mitochondrial haplogroup distributions in self-identified Mexican Americans separately from Hispanic Americans of other descent. We observed clear differences in the distribution of maternal genetic ancestry consistent with proposed admixture models for these subpopulations, underscoring the genetic heterogeneity of the United States Hispanic population. The mitochondrial haplogroup distributions in the other self-identified racial/ethnic groups within NHANES were largely comparable to previous studies. Mitochondrial haplogroup classification was highly concordant with self-identified race/ethnicity (SIRE) in non-Hispanic whites (94.8 %), but was considerably lower in admixed populations including non-Hispanic blacks (88.3 %), Mexican Americans (81.8 %), and other Hispanics (61.6 %), suggesting SIRE does not accurately reflect maternal genetic ancestry, particularly in populations with greater proportions of admixture. Thus, it is important to consider inconsistencies between SIRE and genetic ancestry when performing genetic association studies. The mitochondrial haplogroup data that we have generated, coupled with the epidemiologic variables in NHANES, is a valuable resource for future studies investigating the contribution of mtDNA variation to human health and disease. 相似文献
896.
Grace Y. Sun Dennis Y. Chuang Yijia Zong Jinghua Jiang James C. M. Lee Zezong Gu Agnes Simonyi 《Molecular neurobiology》2014,50(1):6-14
Phospholipases A2 (PLA2s) are important enzymes for the metabolism of fatty acids in membrane phospholipids. Among the three major classes of PLA2s in the mammalian system, the group IV calcium-dependent cytosolic PLA2 alpha (cPLA2α) has received the most attention because it is widely expressed in nearly all mammalian cells and its active participation in cell metabolism. Besides Ca2+ binding to its C2 domain, this enzyme can undergo a number of cell-specific post-translational modifications, including phosphorylation by protein kinases, S-nitrosylation through interaction with nitric oxide (NO), as well as interaction with other proteins and lipid molecules. Hydrolysis of phospholipids by cPLA2 yields two important lipid mediators, arachidonic acid (AA) and lysophospholipids. While AA is known to serve as a substrate for cyclooxygenases and lipoxygenases, which are enzymes for the synthesis of eicosanoids and leukotrienes, lysophospholipids are known to possess detergent-like properties capable of altering microdomains of cell membranes. An important feature of cPLA2 is its link to cell surface receptors that stimulate signaling pathways associated with activation of protein kinases and production of reactive oxygen species (ROS). In the central nervous system (CNS), cPLA2 activation has been implicated in neuronal excitation, synaptic secretion, apoptosis, cell-cell interaction, cognitive and behavioral function, oxidative-nitrosative stress, and inflammatory responses that underline the pathogenesis of a number of neurodegenerative diseases. However, the types of extracellular agonists that target intracellular signaling pathways leading to cPLA2 activation among different cell types and under different physiological and pathological conditions have not been investigated in detail. In this review, special emphasis is given to metabolic events linking cPLA2 to activation in neurons, astrocytes, microglial cells, and cerebrovascular cells. Understanding the molecular mechanism(s) for regulation of this enzyme is deemed important in the development of new therapeutic targets for the treatment and prevention of neurodegenerative diseases. 相似文献
897.
898.
Jeanne C. Chambers Bethany A. Bradley Cynthia S. Brown Carla D’Antonio Matthew J. Germino James B. Grace Stuart P. Hardegree Richard F. Miller David A. Pyke 《Ecosystems》2014,17(2):360-375
Alien grass invasions in arid and semi-arid ecosystems are resulting in grass–fire cycles and ecosystem-level transformations that severely diminish ecosystem services. Our capacity to address the rapid and complex changes occurring in these ecosystems can be enhanced by developing an understanding of the environmental factors and ecosystem attributes that determine resilience of native ecosystems to stress and disturbance, and resistance to invasion. Cold desert shrublands occur over strong environmental gradients and exhibit significant differences in resilience and resistance. They provide an excellent opportunity to increase our understanding of these concepts. Herein, we examine a series of linked questions about (a) ecosystem attributes that determine resilience and resistance along environmental gradients, (b) effects of disturbances like livestock grazing and altered fire regimes and of stressors like rapid climate change, rising CO2, and N deposition on resilience and resistance, and (c) interacting effects of resilience and resistance on ecosystems with different environmental conditions. We conclude by providing strategies for the use of resilience and resistance concepts in a management context. At ecological site scales, state and transition models are used to illustrate how differences in resilience and resistance influence potential alternative vegetation states, transitions among states, and thresholds. At landscape scales management strategies based on resilience and resistance—protection, prevention, restoration, and monitoring and adaptive management—are used to determine priority management areas and appropriate actions. 相似文献
899.
900.
Grace Logan Graham L Freimanis David J King Bego?a Valdazo-González Katarzyna Bachanek-Bankowska Nicholas D Sanderson Nick J Knowles Donald P King Eleanor M Cottam 《BMC genomics》2014,15(1)