全文获取类型
收费全文 | 9722篇 |
免费 | 831篇 |
国内免费 | 9篇 |
专业分类
10562篇 |
出版年
2022年 | 58篇 |
2021年 | 134篇 |
2020年 | 77篇 |
2019年 | 122篇 |
2018年 | 123篇 |
2017年 | 99篇 |
2016年 | 191篇 |
2015年 | 289篇 |
2014年 | 328篇 |
2013年 | 424篇 |
2012年 | 549篇 |
2011年 | 499篇 |
2010年 | 308篇 |
2009年 | 290篇 |
2008年 | 442篇 |
2007年 | 438篇 |
2006年 | 418篇 |
2005年 | 430篇 |
2004年 | 410篇 |
2003年 | 409篇 |
2002年 | 381篇 |
2001年 | 125篇 |
2000年 | 106篇 |
1999年 | 125篇 |
1998年 | 144篇 |
1997年 | 81篇 |
1996年 | 99篇 |
1995年 | 83篇 |
1994年 | 98篇 |
1993年 | 84篇 |
1992年 | 105篇 |
1991年 | 115篇 |
1990年 | 98篇 |
1989年 | 84篇 |
1988年 | 71篇 |
1987年 | 84篇 |
1986年 | 77篇 |
1985年 | 73篇 |
1984年 | 108篇 |
1983年 | 86篇 |
1982年 | 101篇 |
1981年 | 90篇 |
1980年 | 112篇 |
1979年 | 75篇 |
1978年 | 94篇 |
1977年 | 85篇 |
1976年 | 78篇 |
1975年 | 71篇 |
1974年 | 73篇 |
1973年 | 82篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
992.
George S. Mahuku María Antonia Henríquez Carmenza Montoya Carlos Jara Henry Teran Stephen Beebe 《Molecular breeding : new strategies in plant improvement》2011,28(1):57-71
Angular leaf spot (ALS) is one of the major diseases of the common bean (Phaseolus vulgaris L.). Different sources of resistance have been identified but few have been characterized. Studies were conducted to elucidate
the inheritance of ALS resistance in the bean accession G10909 and to identify molecular markers linked to these genes. Evaluation
of parental genotypes, F1, F2 and backcross to susceptible parent (Sprite) populations revealed that two dominant and complementary genes conditioned ALS
resistance. Allelism tests showed that the ALS resistance genes in G10909 were different from those in the Mesoamerican cultivars
Mexico 54, MAR 2, G10474 and Cornell 49-242. Three sequence-characterized amplified region (SCAR) markers, PF13310, PF9260 and OPE04709, and a microsatellite, Pv-gaat001, segregated in coupling with the resistance genes in G10909. Pairwise segregation analysis
revealed that markers PF13310, PF9260 and OPE04709 were linked, while Pv-gaat001 segregated in a 9:3:3:1 ratio from all markers. Markers PF13310, PF9260 and OPE04709 were mapped to linkage group B08, and segregated with resistance gene Phg
G10909B
at 4.9, 7.4 and 9.9 cM, respectively. Pv-gaat001, previously mapped to linkage group B04, segregated with resistance gene
Phg
G10909A
at 13 cM. The potential utility of these markers to aid breeding for ALS resistance is discussed. 相似文献
993.
Background
Rodent models have been used extensively to study mammary gland development and for studies of toxicology and carcinogenesis. Mammary gland gross morphology can visualized via the excision of intact mammary gland chains following fixation and staining with carmine using a tissue preparation referred to as a whole mount. Methods are described for the automated collection of digital images from an entire mammary gland whole mount and for the interrogation of digital data using a "masking" technique available with Image-Pro® plus image analysis software (Mediacybernetics. Silver Spring, MD).Results
Parallel to mammographic analysis in humans, measurements of rodent mammary gland density were derived from area-based or volume-based algorithms and included: total circumscribed mammary fat pad mass, mammary epithelial mass, and epithelium-free fat pad mass. These values permitted estimation of absolute mass of mammary epithelium as well as breast density. The biological plausibility of these measurements was evaluated in mammary whole mounts from rats and mice. During mammary gland development, absolute epithelial mass increased linearly without significant changes in mammographic density. Treatment of rodents with tamoxifen, 9-cis-retinoic acid, or ovariectomy, and occurrence of diet induced obesity decreased both absolute epithelial mass and mammographic density. The area and volumetric methods gave similar results.Conclusions
Digital image analysis can be used for screening agents for potential impact on reproductive toxicity or carcinogenesis as well as for mechanistic studies, particularly for cumulative effects on mammary epithelial mass as well as translational studies of mechanisms that explain the relationship between epithelial mass and cancer risk.994.
995.
Choy HA Kelley MM Croda J Matsunaga J Babbitt JT Ko AI Picardeau M Haake DA 《PloS one》2011,6(2):e16879
Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9-11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats. 相似文献
996.
Daveson AJ Jones DM Gaze S McSorley H Clouston A Pascoe A Cooke S Speare R Macdonald GA Anderson R McCarthy JS Loukas A Croese J 《PloS one》2011,6(3):e17366
Background and Aims
The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten.Methods
In a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-naïve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3rd stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant α-gliadin peptide (QE65)-specific systemic interferon-γ-producing cells by ELISpot pre- and post-wheat challenge.Results
Enteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes.Conclusions
Experimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology.Trial Registration
ClinicalTrials.gov NCT00671138相似文献997.
Achan J Tibenderana J Kyabayinze D Mawejje H Mugizi R Mpeka B Talisuna A D'Alessandro U 《PloS one》2011,6(3):e17053
Introduction
Severe malaria is a life-threatening medical emergency and requires prompt and effective treatment to prevent death. There is paucity of published information on current practices of severe malaria case management in sub-Saharan Africa; we evaluated the management practices for severe malaria in Ugandan health facilitiesMethods and Findings
We did a cross sectional survey, using multi-stage sampling methods, of health facilities in 11 districts in the eastern and mid-western parts of Uganda. The study instruments were adapted from the WHO hospital care assessment tools. Between June and August 2009, 105 health facilities were surveyed and 181 health workers and 868 patients/caretakers interviewed. None of the inpatient facilities had all seven components of a basic care package for the management of severe malaria consistently available during the 3 months prior to the survey. Referral practices were appropriate for <10% (18/196) of the patients. Prompt care at any health facility was reported by 29% (247/868) of patients. Severe malaria was correctly diagnosed in 27% of patients (233).Though the quinine dose and regimen was correct in the majority (611/868, 70.4%) of patients, it was administered in the correct volumes of 5% dextrose in only 18% (147/815). Most patients (80.1%) had several doses of quinine administered in one single 500 ml bottle of 5% dextrose. Medications were purchased by 385 (44%) patients and medical supplies by 478 patients (70.6%).Conclusions
Management of severe malaria in Ugandan health facilities was sub-optimal. These findings highlight the challenges of correctly managing severe malaria in resource limited settings. Priority areas for improvement include triage and emergency care, referral practises, quality of diagnosis and treatment, availability of medicines and supplies, training and support supervision. 相似文献998.
Background
Children with complex urogenital anomalies often require bladder reconstruction. Gastrointestinal tissues used in bladder augmentations exhibit a greatly increased risk of malignancy, and the bladder microenvironment may play a role in this carcinogenesis. Investigating the influences of the bladder microenvironment on gastrointestinal and urothelial cell cycle checkpoint activation and DNA damage response has been limited by the lack of an appropriate well-differentiated urothelial cell line system.Methodology/Principal Findings
To meet this need, we have developed a well-differentiated conditionally immortalized urothelial cell line by isolating it from the H-2Kb-tsA58 transgenic mouse. These cells express a thermosensitive SV40 large T antigen that can be deactivated by adjustment of cell culture conditions, allowing the cell line to regain normal control of the cell cycle. The isolated urothelial cell line demonstrates a polygonal, dome-shaped morphology, expresses cytokeratin 18, and exhibits well-developed tight junctions. Adaptation of the urothelial cell line to hyperosmolal culture conditions induces expression of both cytokeratin 20 and uroplakin II, markers of a superficial urothelial cell or “umbrella cell.” This cell line can be maintained indefinitely in culture under permissive conditions but when cultured under non-permissive conditions, large T antigen expression is reduced substantially, leading to increased p53 activity and reduced cellular proliferation.Conclusions/Significance
This new model of urothelial cells, along with gastrointestinal cell lines previously derived from the H-2Kb-tsA58 transgenic mouse, will be useful for studying the potential mechanisms of carcinogenesis of the augmented bladder. 相似文献999.
Background
Exploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD) and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM), a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD.Methodology and Principal Findings
Twelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability) patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions.Conclusions/Significance
Manic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design to characterize exploration and novelty seeking and, in parallel with animal studies, can contribute to developing treatments that target neuropsychiatric disease. 相似文献1000.
Davis JL Huang L Worodria W Masur H Cattamanchi A Huber C Miller C Conville PS Murray P Kovacs JA 《PloS one》2011,6(1):e16321