全文获取类型
收费全文 | 1901篇 |
免费 | 181篇 |
国内免费 | 5篇 |
出版年
2021年 | 22篇 |
2020年 | 14篇 |
2019年 | 15篇 |
2018年 | 20篇 |
2017年 | 19篇 |
2016年 | 28篇 |
2015年 | 61篇 |
2014年 | 70篇 |
2013年 | 90篇 |
2012年 | 95篇 |
2011年 | 119篇 |
2010年 | 62篇 |
2009年 | 49篇 |
2008年 | 77篇 |
2007年 | 103篇 |
2006年 | 91篇 |
2005年 | 96篇 |
2004年 | 70篇 |
2003年 | 76篇 |
2002年 | 66篇 |
2001年 | 56篇 |
2000年 | 51篇 |
1999年 | 57篇 |
1998年 | 27篇 |
1997年 | 13篇 |
1996年 | 22篇 |
1995年 | 22篇 |
1994年 | 20篇 |
1993年 | 28篇 |
1992年 | 32篇 |
1991年 | 27篇 |
1990年 | 34篇 |
1989年 | 27篇 |
1988年 | 19篇 |
1987年 | 30篇 |
1986年 | 25篇 |
1985年 | 27篇 |
1984年 | 32篇 |
1983年 | 15篇 |
1982年 | 25篇 |
1981年 | 20篇 |
1980年 | 22篇 |
1979年 | 22篇 |
1978年 | 12篇 |
1977年 | 16篇 |
1976年 | 13篇 |
1975年 | 13篇 |
1974年 | 18篇 |
1973年 | 11篇 |
1972年 | 11篇 |
排序方式: 共有2087条查询结果,搜索用时 15 毫秒
111.
David J. Lea-Smith Maite L. Ortiz-Suarez Tchern Lenn Dennis J. Nürnberg Laura L. Baers Matthew P. Davey Lucia Parolini Roland G. Huber Charles A. R. Cotton Giulia Mastroianni Paolo Bombelli Petra Ungerer Tim J. Stevens Alison G. Smith Peter J. Bond Conrad W. Mullineaux Christopher J. Howe 《Plant physiology》2016,172(3):1928-1940
Cyanobacteria are intricately organized, incorporating an array of internal thylakoid membranes, the site of photosynthesis, into cells no larger than other bacteria. They also synthesize C15-C19 alkanes and alkenes, which results in substantial production of hydrocarbons in the environment. All sequenced cyanobacteria encode hydrocarbon biosynthesis pathways, suggesting an important, undefined physiological role for these compounds. Here, we demonstrate that hydrocarbon-deficient mutants of Synechococcus sp. PCC 7002 and Synechocystis sp. PCC 6803 exhibit significant phenotypic differences from wild type, including enlarged cell size, reduced growth, and increased division defects. Photosynthetic rates were similar between strains, although a minor reduction in energy transfer between the soluble light harvesting phycobilisome complex and membrane-bound photosystems was observed. Hydrocarbons were shown to accumulate in thylakoid and cytoplasmic membranes. Modeling of membranes suggests these compounds aggregate in the center of the lipid bilayer, potentially promoting membrane flexibility and facilitating curvature. In vivo measurements confirmed that Synechococcus sp. PCC 7002 mutants lacking hydrocarbons exhibit reduced thylakoid membrane curvature compared to wild type. We propose that hydrocarbons may have a role in inducing the flexibility in membranes required for optimal cell division, size, and growth, and efficient association of soluble and membrane bound proteins. The recent identification of C15-C17 alkanes and alkenes in microalgal species suggests hydrocarbons may serve a similar function in a broad range of photosynthetic organisms.Cyanobacteria (oxygenic photosynthetic bacteria) are found in nearly every environment on Earth and are major contributors to global carbon and nitrogen fixation (Galloway et al., 2004; Zwirglmaier et al., 2008). They are distinguished among prokaryotes in containing multiple internal thylakoid membranes, the site of photosynthesis, and a large protein compartment, the carboxysome, involved in carbon fixation. Despite these extra features, cyanobacteria can be as small as 0.6 µm in diameter (Raven, 1998).All cyanobacteria with sequenced genomes encode the pathway for the biosynthesis of hydrocarbons, implying an important, although as-yet-undefined, role for these compounds (Lea-Smith et al., 2015). The major forms are C15-C19 alkanes and alkenes, which can be synthesized from fatty acyl-acyl-carrier proteins (ACPs) by one or other of two separate pathways (Fig. 1; Schirmer et al., 2010; Mendez-Perez et al., 2011). The majority of species produce alkanes and alkenes via acyl-ACP reductase (FAR) and aldehyde deformylating oxygenase (FAD; Schirmer et al., 2010; Li et al., 2012; Coates et al., 2014; Lea-Smith et al., 2015). Cyanobacterial species lacking the FAR/FAD pathway synthesize alkenes via olefin synthase (Ols; Mendez-Perez et al., 2011; Coates et al., 2014; Lea-Smith et al., 2015). This suggests that hydrocarbons produced by either pathway serve a similar role in the cell. Homologs of FAR/FAD or Ols are not present in other bacteria or plant and algal species. However, C15-C17 alkanes and alkenes, synthesized by an alternate, uncharacterized pathway, were recently detected in a range of green microalgae, including Chlamydomonas reinhardtii, Chlorella variabilis NC64A, and several Nannochloropsis species (Sorigué et al., 2016). In C. reinhardtii, hydrocarbons were primarily localized to the chloroplast, which originated in evolution from a cyanobacterium that was engulfed by a host organism (Howe et al., 2008). Hydrocarbons may therefore have a similar role in cyanobacteria, some green microalgae species, and possibly a broader range of photosynthetic organisms.Open in a separate windowFigure 1.Hydrocarbon biosynthesis is encoded in all sequenced cyanobacteria. Detailed are the two hydrocarbon biosynthetic pathways, indicated in blue and red, respectively, in cyanobacteria. The number of species encoding the enzymes in each pathway is indicated.Hydrocarbons act as antidesiccants, waterproofing agents, and signaling molecules in insects (Howard and Blomquist, 2005) and prevent water loss, ensure pollen viability, and influence pathogen interactions in plants (Kosma et al., 2009; Bourdenx et al., 2011). However, the function of hydrocarbons in cyanobacteria has not been determined. Characterization of cyanobacterial hydrocarbon biosynthesis pathways has provided the basis for investigating synthetic microbial biofuel systems, which may be a renewable substitute for fossil fuels (Schirmer et al., 2010; Choi and Lee, 2013; Howard et al., 2013). However, secretion of long-chain hydrocarbons from the cell into the medium, which is likely essential for commercially viable production, has not been observed in the absence of a membrane solubilization agent (Schirmer et al., 2010; Tan et al., 2011). Cyanobacterial hydrocarbons also have a significant environmental role. Due to the abundance of cyanobacteria in the environment, hydrocarbon production is considerable, with hundreds of millions of tons released into the ocean per annum following cell death (Lea-Smith et al., 2015). This production may be sufficient to sustain populations of hydrocarbon-degrading bacteria, which can then play an important role in consuming anthropogenic oil spills (Lea-Smith et al., 2015).Here, we investigated the cellular location and role of hydrocarbons in both spherical Synechocystis sp. PCC 6803 (Synechocystis) and rod-shaped Synechococcus sp. PCC 7002 (Synechococcus) cells. We developed a model of the cyanobacterial membrane, which indicated that hydrocarbons aggregate in the middle of the lipid bilayer and, when present at levels observed in cells, lead to membrane swelling associated with pools of hydrocarbon. This suggested that alkanes may facilitate membrane curvature. In vivo measurements of Synechococcus thylakoid membrane conformation are consistent with this model. 相似文献
112.
113.
Conrad W. Speed Matthew J. Rees Katherine Cure Brigit Vaughan Mark G. Meekan 《Ecology and evolution》2019,9(18):10553-10566
The recovery of communities of predatory fishes within a no‐take marine reserve after the eradication of illegal fishing provides an opportunity to examine the role of sharks and other large‐bodied mesopredatory fishes in structuring reef fish communities. We used baited remote underwater video stations to investigate whether an increase in sharks was associated with a change in structure of the mesopredatory fish community at Ashmore Reef, Western Australia. We found an almost fourfold increase in shark abundance in reef habitat from 0.64 hr?1 ± 0.15 SE in 2004, when Ashmore Reef was being fished illegally, to 2.45 hr?1 ± 0.37 in 2016, after eight years of full‐time enforcement of the reserve. Shark recovery in reef habitat was accompanied by a two and a half‐fold decline in the abundance of small mesopredatory fishes (≤50 cm TL) (14.00 hr?1 ± 3.79 to 5.6 hr?1 ± 1.20) and a concomitant increase in large mesopredatory fishes (≥100 cm TL) from 1.82 hr?1 ± 0.48 to 4.27 hr?1 ± 0.93. In contrast, near‐reef habitats showed an increase in abundance of large mesopredatory fishes between years (2.00 hr?1 ± 0.65 to 4.56 hr?1 ± 1.11), although only smaller increases in sharks (0.67 hr?1 ± 0.25 to 1.22 hr?1 ± 0.34) and smaller mesopredatory fishes. Although the abundance of most mesopredatory groups increased with recovery from fishing, we suggest that the large decline of small mesopredatory fish in reef habitat was mostly due to higher predation pressure following the increase in sharks and large mesopredatory fishes. At the regional scale, the structure of fished communities at Ashmore Reef in 2004 resembled those of present day Scott Reefs, where fishing still continues today. In 2016, Ashmore fish communities resembled those of the Rowley Shoals, which have been protected from fishing for decades. 相似文献
114.
115.
Estrogens are required for the proliferation of hormone dependent breast cancer cells, making estrogen receptor (ER) positive tumors amenable to endocrine therapies such as antiestrogens. However, resistance to these agents remains a significant cause of treatment failure. We previously demonstrated that inactivation of the retinoblastoma protein (pRb) family tumor suppressors causes antiestrogen resistance in MCF-7 cells, a widely studied model of estrogen responsive human breast cancers. In this study, we investigate the mechanism by which pRb inactivation leads to antiestrogen resistance. Cdk4 and cdk2 are two key cell cycle regulators that can phosphorylate and inactivate pRb, therefore we tested whether these kinases are required in cells lacking pRb function. pRb family members were inactivated in MCF-7 cells by expressing polyomavirus large tumor antigen (PyLT), and cdk activity was inhibited using the cdk inhibitors p16(INK4A) and p21(Waf1/Cip1). Cdk4 activity was no longer required in cells lacking functional pRb, while cdk2 activity was required for proliferation in both the presence and absence of pRb function. Using inducible PyLT cell lines, we further demonstrated that pRb inactivation leads to increased cyclin A expression, cdk2 activation and proliferation in antiestrogen arrested cells. These results demonstrate that antiestrogens do not inhibit cdk2 activity or proliferation of MCF-7 cells in the absence of pRb family function, and suggest that antiestrogen resistant breast cancer cells resulting from pRb pathway inactivation would be susceptible to therapies that target cdk2. 相似文献
116.
Goldman AS Guisinger VH Aikins M Amarillo ML Belizario VY Garshong B Gyapong J Kabali C Kamal HA Kanjilal S Kyelem D Lizardo J Malecela M Mubyazi G Nitièma PA Ramzy RM Streit TG Wallace A Brady MA Rheingans R Ottesen EA Haddix AC 《PLoS neglected tropical diseases》2007,1(1):e67
Background
Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk.Methodology/Principal Findings
To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications.Conclusions/Significance
MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones. 相似文献117.
As proteomic MS has increased in throughput, so has the demand to catalogue the increasing number of peptides and proteins observed by the community using this technique. As in other 'omics' fields, this brings obvious scientific benefits such as sharing of results and prevention of unnecessary repetition, but also provides technical insights, such as the ability to compare proteome coverage between different laboratories, or between different proteomic platforms. Journals are also moving towards mandating that proteomics data be submitted to public repositories upon publication. In response to these demands, several web-based repositories have been established to store protein and peptide identifications derived from MS data, and a similar number of peptide identification software pipelines have emerged to deliver identifications to these repositories. This paper reviews the latest developments in public domain peptide and protein identification databases and describes the analysis pipelines that feed them. Recent applications of the tools to pertinent biological problems are examined, and through comparing and contrasting the capabilities of each system, the issues facing research users of web-based repositories are explored. Future developments and mechanisms to enhance system functionality and user-interfacing opportunities are also suggested. 相似文献
118.
119.
Organisms Diversity & Evolution - Chaetopteridae — the parchment worms — comprise a group of early branching annelids with a scarcely investigated neuroanatomy and neurogenesis. Due... 相似文献
120.
Andrea Swei Kerry E. OConnor Lisa I. Couper Jose Thekkiniath Patricia A. Conrad Kerry A. Padgett Joseph Burns Melissa H. Yoshimizu Ben Gonzales Brandon Munk Nicholas Shirkey Lora Konde Choukri Ben Mamoun Robert S. Lane Anne Kjemtrup 《International journal for parasitology》2019,49(2):95-103
Babesiosis is a potentially fatal tick-borne zoonotic disease caused by a species complex of blood parasites that can infect a variety of vertebrates, particularly dogs, cattle, and humans. In the United States, human babesiosis is caused by two distinct parasites, Babesia microti and Babesia duncani. The enzootic cycle of B. microti, endemic in the northeastern and upper midwestern regions, has been well characterised. In the western United States, however, the natural reservoir host and tick vector have not been identified for B. duncani, greatly impeding efforts to understand and manage this zoonotic disease. Two and a half decades after B. duncani was first described in a human patient in Washington State, USA, we provide evidence that the enzootic tick vector is the winter tick, Dermacentor albipictus, and the reservoir host is likely the mule deer, Odocoileus hemionus. The broad, overlapping ranges of these two species covers a large portion of far-western North America, and is consistent with confirmed cases of B. duncani in the far-western United States. 相似文献