全文获取类型
收费全文 | 6977篇 |
免费 | 614篇 |
国内免费 | 1篇 |
出版年
2024年 | 11篇 |
2023年 | 33篇 |
2022年 | 83篇 |
2021年 | 203篇 |
2020年 | 92篇 |
2019年 | 117篇 |
2018年 | 157篇 |
2017年 | 130篇 |
2016年 | 235篇 |
2015年 | 456篇 |
2014年 | 486篇 |
2013年 | 470篇 |
2012年 | 659篇 |
2011年 | 629篇 |
2010年 | 356篇 |
2009年 | 302篇 |
2008年 | 469篇 |
2007年 | 446篇 |
2006年 | 398篇 |
2005年 | 369篇 |
2004年 | 332篇 |
2003年 | 346篇 |
2002年 | 286篇 |
2001年 | 48篇 |
2000年 | 34篇 |
1999年 | 68篇 |
1998年 | 64篇 |
1997年 | 44篇 |
1996年 | 40篇 |
1995年 | 35篇 |
1994年 | 23篇 |
1993年 | 31篇 |
1992年 | 22篇 |
1991年 | 13篇 |
1990年 | 18篇 |
1989年 | 8篇 |
1988年 | 9篇 |
1987年 | 9篇 |
1986年 | 4篇 |
1985年 | 10篇 |
1984年 | 8篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 2篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
排序方式: 共有7592条查询结果,搜索用时 15 毫秒
171.
Summary A large number of projects have recently been initiated in Scotland aiming to restore native woodland, which are being undertaken by a variety of organisations, often in partnership, with environmental NGOs playing a leading role. The objectives, constraints and methodologies of these projects are critically reviewed, partly through a questionnaire survey. Most aim to restore ‘natural’ woodland, but the lack of appropriate reference ecosystems and uncertainty about the characteristics of the original forest hinder the development of precise objectives, and consequently the criteria for success are poorly defined. Most projects face major practical constraints, particularly browsing by herbivores and invasion by exotic species, indicating that they will require long-term management interventions. Most woodlands are isolated from other woodlands, which threatens their long-term viability, restricting colonisation by woodland organisms. Greater reference to ecological theory in practical restoration projects such as these would enable objectives to be defined with more precision, encourage a greater emphasis on ecological processes rather than community composition, and improve management plans through use of predictive tools. In particular, the integration of woodlands into habitat networks, increasing ecological connectivity between woodland fragments, is considered essential to ensure success in the long term. 相似文献
172.
Vicky Wang-Wei Tsai Laurence Macia Heiko Johnen Tamara Kuffner Rakesh Manadhar Sebastian Beck J?rgensen Ka Ki Michelle Lee-Ng Hong Ping Zhang Liyun Wu Christopher Peter Marquis Lele Jiang Yasmin Husaini Shu Lin Herbert Herzog David A. Brown Amanda Sainsbury Samuel N. Breit 《PloS one》2013,8(2)
The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1−/−) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1−/− mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1−/− mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage. 相似文献
173.
Laura N. Anderson Michelle Cotterchio Julia A. Knight Ayelet Borgida Steven Gallinger Sean P. Cleary 《PloS one》2013,8(6)
Recent studies of 25-hydroxyvitamin D (25(OH)D) levels and pancreas cancer have suggested a potential role of the vitamin D pathway in the etiology of this fatal disease. Variants in vitamin-D related genes are known to affect 25(OH)D levels and function and it is unknown if these variants may influence pancreatic cancer risk. The association between 87 single nucleotide polymorphisms (SNPs) in 11 genes was evaluated within the Ontario Pancreas Cancer Study, a population-based case-control study. Pancreatic cancer cases with pathology confirmed adenocarcinoma were identified from the Ontario Cancer Registry (n = 628) and controls were identified through random digit dialing (n = 1193). Age and sex adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. SNPs in the CYP24A1, CYP2R1, calcium sensing receptor (CASR), vitamin D binding protein (GC), retinoid X receptor-alpha (RXRA) and megalin (LRP2) genes were significantly associated with pancreas cancer risk. For example, pancreas cancer risk was inversely associated with CYP2R1 rs10741657 (AA versus GG, OR = 0.70; 95%CI: 0.51–0.95) and positively with CYP24A1 rs6127119 (TT versus CC. OR = 1.94; 95%CI: 1.28–2.94). None of the associations were statistically significant after adjustment for multiple comparisons. Vitamin D pathway gene variants may be associated with pancreas cancer risk and future studies are needed to understand the possible role of vitamin D in tumorigenesis and may have implications for cancer-prevention strategies. 相似文献
174.
Gregory J. Tanner Michelle L. Colgrave Malcolm J. Blundell Hareshwar P. Goswami Crispin A. Howitt 《PloS one》2013,8(2)
Background
Subjects suffering from coeliac disease, gluten allergy/intolerance must adopt a lifelong avoidance of gluten. Beer contains trace levels of hordeins (gluten) which are too high to be safely consumed by most coeliacs. Accurate measurement of trace hordeins by ELISA is problematic.Methods
We have compared hordein levels in sixty beers, by sandwich ELISA, with the level determined using multiple reaction monitoring mass spectrometry (MRM-MS).Results
Hordein levels measured by ELISA varied by four orders of magnitude, from zero (for known gluten-free beers) to 47,000 µg/mL (ppm; for a wheat-based beer). Half the commercial gluten-free beers were free of hordein by MS and ELISA. Two gluten-free and two low-gluten beers had zero ELISA readings, but contained significant hordein levels (p<0.05), or near average (60–140%) hordein levels, by MS, respectively. Six beers gave false negatives, with zero ELISA readings but near average hordein content by MS. Approximately 20% of commercial beers had ELISA readings less than 1 ppm, but a near average hordein content by MS. Several barley beers also contained undeclared wheat proteins.Conclusions
ELISA results did not correlate with the relative content of hordein peptides determined by MS, with all barley based beers containing hordein. We suggest that mass spectrometry is more reliable than ELISA, as ELISA enumerates only the concentration of particular amino-acid epitopes; this may vary between different hordeins and may not be related to the absolute hordein concentration. MS quantification is undertaken using peptides that are specific and unique, enabling the quantification of individual hordein isoforms. This outlines the problem of relying solely on ELISA determination of gluten in beverages such as beer and highlights the need for the development of new sensitive and selective quantitative assay such as MS. 相似文献175.
Background
Progress toward meeting Millennium Development Goal 5, which aims to improve maternal and reproductive health outcomes, is behind schedule. This is despite ever increasing volumes of official development aid targeting the goal, calling into question the distribution and efficacy of aid. The 2005 Paris Declaration on Aid Effectiveness represented a global commitment to reform aid practices in order to improve development outcomes, encouraging a shift toward collaborative aid arrangements which support the national plans of aid recipient countries (and discouraging unaligned donor projects).Methods and Findings
We conducted a systematic review to summarise the evidence of the impact on MDG 5 outcomes of official development aid delivered in line with Paris aid effectiveness principles and to compare this with the impact of aid in general on MDG 5 outcomes. Searches of electronic databases identified 30 studies reporting aid-funded interventions designed to improve maternal and reproductive health outcomes. Aid interventions appear to be associated with small improvements in the MDG indicators, although it is not clear whether changes are happening because of the manner in which aid is delivered. The data do not allow for a meaningful comparison between Paris style and general aid. The review identified discernible gaps in the evidence base on aid interventions targeting MDG 5, notably on indicators MDG 5.4 (adolescent birth rate) and 5.6 (unmet need for family planning).Discussion
This review presents the first systematic review of the impact of official development aid delivered according to the Paris principles and aid delivered outside this framework on MDG 5 outcomes. Its findings point to major gaps in the evidence base and should be used to inform new approaches and methodologies aimed at measuring the impact of official development aid. 相似文献176.
Michelle A. Arya Albert K. Tai Eric C. Wooten Christopher D. Parkin Elena Kudryavtseva Gordon S. Huggins 《PloS one》2013,8(8)
The loss of muscle mass in alcoholic myopathy may reflect alcohol inhibition of myogenic cell differentiation into myotubes. Here, using a high content imaging system we show that ethanol inhibits C2C12 myoblast differentiation by reducing myogenic fusion, creating smaller and less complex myotubes compared with controls. Ethanol administration during C2C12 differentiation reduced MyoD and myogenin expression, and microarray analysis identified ethanol activation of the Notch signaling pathway target genes Hes1 and Hey1. A reporter plasmid regulated by the Hes1 proximal promoter was activated by alcohol treatment in C2C12 cells. Treatment of differentiating C2C12 cells with a gamma secretase inhibitor (GSI) abrogated induction of Hes1. On a morphological level GSI treatment completely rescued myogenic fusion defects and partially restored other myotube parameters in response to alcohol. We conclude that alcohol inhibits C2C12 myoblast differentiation and the inhibition of myogenic fusion is mediated by Notch pathway activation. 相似文献
177.
Nam P. Nguyen Lexie Smith-Raymond Vincent Vinh-Hung Paul Vos Rick Davis Anand Desai Thomas Sroka Dave Abraham Shane P. Krafft Michelle Stevie Homayoun Modarresifar Beng-Hoey Jo Misty Ceizyk 《PloS one》2013,8(3)
Purpose
The study aims to assess the feasibility of Tomotherapy-based image-guided radiotherapy (IGRT) to reduce the aspiration risk in patients with non-laryngeal and non-hypopharyngeal cancer. A retrospective review of 48 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers was conducted. All patients had a modified barium swallow (MBS) prior to treatment, which was repeated one month following radiotherapy. Mean middle and inferior pharyngeal dose was recorded and correlated with the MBS results to determine aspiration risk.Results
Mean pharyngeal dose was 23.2 Gy for the whole group. Two patients (4.2%) developed trace aspiration following radiotherapy which resolved with swallowing therapy. At a median follow-up of 19 months (1–48 months), all patients were able to resume normal oral feeding without aspiration.Conclusion and Clinical Relevance
IGRT may reduce the aspiration risk by decreasing the mean pharyngeal dose in the presence of large cervical lymph nodes. Further prospective studies with IGRT should be performed in patients with non-laryngeal and non-hypopharyngeal head and neck cancers to verify this hypothesis. 相似文献178.
Jiannong Xu Julián F. Hillyer Boubacar Coulibaly Madjou Sacko Adama Dao Oumou Niaré Michelle M. Riehle Sekou F. Traoré Kenneth D. Vernick 《PloS one》2013,8(4)
Background
Malaria parasites undergo complex developmental transitions within the mosquito vector. A commonly used laboratory model for studies of mosquito-malaria interaction is the rodent parasite, P. berghei. Anopheles funestus is a major malaria vector in sub-Saharan Africa but has received less attention than the sympatric species, Anopheles gambiae. The imminent completion of the A. funestus genome sequence will provide currently lacking molecular tools to describe malaria parasite interactions in this mosquito, but previous reports suggested that A. funestus is not permissive for P. berghei development.Methods
An A. funestus population was generated in the laboratory by capturing female wild mosquitoes in Mali, allowing them to oviposit, and rearing the eggs to adults. These F1 progeny of wild mosquitoes were allowed to feed on mice infected with a fluorescent P. berghei strain. Fluorescence microscopy was used to track parasite development inside the mosquito, salivary gland sporozoites were tested for infectivity to mice, and parasite development in A. funestus was compared to A. gambiae.Results
P. berghei oocysts were detectable on A. funestus midguts by 7 days post-infection. By 18–20 days post-infection, sporozoites had invaded the median and distal lateral lobes of the salivary glands, and hemocoel sporozoites were observed in the hemolymph. Mosquitoes were capable of infecting mice via bite, demonstrating that A. funestus supports the complete life cycle of P. berghei. In a random sample of wild mosquito genotypes, A. funestus prevalence of infection and the characteristics of parasite development were similar to that observed in A. gambiae-P. berghei infections.Conclusions
The data presented in this study establish an experimental laboratory model for Plasmodium infection of A. funestus, an important vector of human malaria. Studying A. funestus-Plasmodium interactions is now feasible in a laboratory setting. This information lays the groundwork for exploitation of the awaited genome sequence of A. funestus. 相似文献179.
Ruchi Mathur Gene Kim Walter Morales Jaekyu Sung Emily Rooks Venkata Pokkunuri Stacy Weitsman Gillian M. Barlow Christopher Chang Mark Pimentel 《Obesity (Silver Spring, Md.)》2013,21(4):748-754
It is increasingly understood that gastrointestinal (GI) methanogens, including Methanobrevibacter smithii, influence host metabolism.
Objective:
Therefore, we compared M. smithii colonization and weight gain in a rat model under different dietary conditions.Design and Methods:
Sprague‐Dawley rats were inoculated with M. smithii or vehicle (N = 10/group), fed normal chow until day 112 postinoculation, high‐fat chow until day 182, then normal chow until day 253. Thereafter, five rats from each group were fed high‐fat and normal chow until euthanasia.Results:
Both groups exhibited M. smithii colonization, which increased following inoculation only for the first 9 days. Change to high‐fat chow correlated with significant increases in weight (P < 0.00001) and stool M. smithii (P < 0.01) in all rats, with stool M. smithi decreasing on return to normal chow. Rats switched back to high‐fat on day 253 further increased weight (P < 0.001) and stool M. smithii (P = 0.039). Euthanasia revealed all animals had higher M. smithii, but not total bacteria, in the small intestine than in the colon. Rats switched back to high‐fat chow had higher M. smithii levels in the duodenum, ileum, and cecum than those fed normal chow; total bacteria did not differ in any bowel segment. Rats which gained more weight had more bowel segments colonized, and the lowest weight recorded was in a rat on high‐fat chow which had minimal M. smithii colonization.Conclusions:
We conclude that M. smithii colonization occurs in the small bowel as well as in the colon, and that the level and extent of M. smithii colonization is predictive of degree of weight gain in this animal model. 相似文献180.
Rebecca C. Holmberg Alissa Gindlesperger Tinsley Stokes David Lopez Lynn Hyman Michelle Freed Phil Belgrader Jeanne Harvey Zheng Li 《PloS one》2013,8(8)
Due to the low percentage of fetal DNA present in maternal plasma (< 10%) during early gestation, efficient extraction processes are required for successful downstream detection applications in non-invasive prenatal diagnostic testing. In this study, two extraction methods using similar chemistries but different workflows were compared for isolation efficiency and percent fetal DNA recovery. The Akonni Biosystems TruTip technology uses a binding matrix embedded in a pipette tip; the Circulating Nucleic Acids Kit from Qiagen employs a spin column approach. The TruTip method adds an extra step to decrease the recovery of DNA fragments larger than 600 bp from the sample to yield an overall higher percentage of smaller molecular weight DNA, effectively enriching for fetal DNA. In this evaluation, three separate extraction comparison studies were performed - a dilution series of fragmented DNA in plasma, a set of clinical maternal samples, and a blood collection tube time point study of maternal samples. Both extraction methods were found to efficiently extract small fragment DNA from large volumes of plasma. In the amended samples, the TruTip extraction method was ~15% less efficient with overall DNA recovery, but yielded an 87% increase in % fetal DNA relative to the Qiagen method. The average percent increase of fetal DNA of TruTip extracted samples compared to the Qiagen method was 55% for all sets of blinded clinical samples. A study comparing extraction efficiencies from whole blood samples incubated up to 48 hours prior to processing into plasma resulted in more consistent % fetal DNA recoveries using TruTip. The extracted products were tested on two detection platforms, quantitative real-time PCR and droplet digital PCR, and yielded similar results for both extraction methods. 相似文献