全文获取类型
收费全文 | 4630篇 |
免费 | 334篇 |
国内免费 | 1篇 |
专业分类
4965篇 |
出版年
2023年 | 24篇 |
2022年 | 49篇 |
2021年 | 89篇 |
2020年 | 59篇 |
2019年 | 64篇 |
2018年 | 96篇 |
2017年 | 88篇 |
2016年 | 155篇 |
2015年 | 205篇 |
2014年 | 226篇 |
2013年 | 315篇 |
2012年 | 373篇 |
2011年 | 355篇 |
2010年 | 226篇 |
2009年 | 195篇 |
2008年 | 289篇 |
2007年 | 303篇 |
2006年 | 269篇 |
2005年 | 251篇 |
2004年 | 215篇 |
2003年 | 193篇 |
2002年 | 199篇 |
2001年 | 48篇 |
2000年 | 24篇 |
1999年 | 42篇 |
1998年 | 62篇 |
1997年 | 25篇 |
1996年 | 37篇 |
1995年 | 45篇 |
1994年 | 24篇 |
1993年 | 39篇 |
1992年 | 28篇 |
1991年 | 26篇 |
1990年 | 18篇 |
1989年 | 11篇 |
1988年 | 12篇 |
1987年 | 24篇 |
1986年 | 16篇 |
1985年 | 18篇 |
1984年 | 15篇 |
1983年 | 15篇 |
1982年 | 16篇 |
1981年 | 17篇 |
1980年 | 18篇 |
1977年 | 10篇 |
1976年 | 12篇 |
1975年 | 16篇 |
1974年 | 11篇 |
1973年 | 11篇 |
1972年 | 11篇 |
排序方式: 共有4965条查询结果,搜索用时 15 毫秒
101.
Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene 总被引:6,自引:0,他引:6 下载免费PDF全文
Digilio MC Conti E Sarkozy A Mingarelli R Dottorini T Marino B Pizzuti A Dallapiccola B 《American journal of human genetics》2002,71(2):389-394
Multiple-lentigines (ML)/LEOPARD (multiple lentigines, electrocardiographic-conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness) syndrome is an autosomal dominant condition--characterized by lentigines and café au lait spots, facial anomalies, cardiac defects--that shares several clinical features with Noonan syndrome (NS). We screened nine patients with ML/LEOPARD syndrome (including a mother-daughter pair) and two children with NS who had multiple café au lait spots, for mutations in the NS gene, PTPN11, and found, in 10 of 11 patients, one of two new missense mutations, in exon 7 or exon 12. Both mutations affect the PTPN11 phosphotyrosine phosphatase domain, which is involved in <30% of the NS PTPN11 mutations. The study demonstrates that ML/LEOPARD syndrome and NS are allelic disorders. The detected mutations suggest that distinct molecular and pathogenetic mechanisms cause the peculiar cutaneous manifestations of the ML/LEOPARD-syndrome subtype of NS. 相似文献
102.
Raquel Portela Catarina R. Leal Pedro L. Almeida Rita G. Sobral 《Microbial biotechnology》2019,12(4):586-610
Although several therapeutic approaches are available for wound and burn treatment and much progress has been made in this area, room for improvement still exists, driven by the urgent need of better strategies to accelerate wound healing and recovery, mostly for cases of severe burned patients. Bacterial cellulose (BC) is a biopolymer produced by bacteria with several advantages over vegetal cellulose, such as purity, high porosity, permeability to liquid and gases, elevated water uptake capacity and mechanical robustness. Besides its biocompatibility, BC can be modified in order to acquire antibacterial response and possible local drug delivery features. Due to its intrinsic versatility, BC is the perfect example of a biotechnological response to a clinical problem. In this review, we assess the BC main features and emphasis is given to a specific biomedical application: wound dressings. The production process and the physical–chemical properties that entitle this material to be used as wound dressing namely for burn healing are highlighted. An overview of the most common BC composites and their enhanced properties, in particular physical and biological, is provided, including the different production processes. A particular focus is given to the biochemistry and genetic manipulation of BC. A summary of the current marketed BC-based wound dressing products is presented, and finally, future perspectives for the usage of BC as wound dressing are foreseen. 相似文献
103.
V Coiro L Capretti L Bianconi A Castelli L Cerri G Roberti A Marcato R Volpi P Chiodera 《Hormones et métabolisme》1991,23(12):600-604
The effects of sodium valproate (a drug enhancing endogenous gamma aminobutyric acid (GABA)-ergic activity) and of the GABA analog baclofen (a GABA B receptor agonist) on serum GH levels was tested in 8 type I diabetic men and 8 normal controls. Sodium valproate (800 mg) or baclofen (10 mg) were given by mouth at 08.30 h on the experimental day. Control tests with a placebo were performed on different occasions. Basal GH levels were similar in controls and diabetic patients. Sodium valproate induced a 7 fold increase in serum GH concentrations in both groups. In contrast, baclofen-induced GH rise was significantly higher in normal controls (mean peak was 3.4 times higher than baseline) than in diabetic patients (mean peak was only 2.1 times higher than basal value). Serum GH levels did not change after placebo administration in any groups. These data suggest the presence of diabetes-induced alterations of a GABAergic pathway mediated by B receptors in the control of GH secretion. Alternatively, the data might indicate a change in diabetic men of other baclofen-sensitive neurotransmissions, different from GABA. 相似文献
104.
Characterization of a Marine Bacterium Associated with Crassostrea virginica (the Eastern Oyster) 总被引:2,自引:6,他引:2 下载免费PDF全文
A gram-negative bacterium found to be closely associated with oysters has been isolated and characterized. The organism, designated LST, has a generation time of 106 min in Marine broth under optimal growth conditions at 25°C. During the decline phase of growth, it exhibits a morphological transition from a motile rod (ca. 1 μm in length) to an elongated, 3- to 40-μm, nonmotile, tightly coiled helix. LST synthesizes and releases a pigment in the stationary and decline phases of growth. Identified as melanin on the basis of chemical properties and UV absorbance maxima, the pigment comprises polymers of heterogeneous molecular weights, ranging from 12,000 to 120,000. The guanosine-plus-cytosine content of the LST DNA is 46%, and results of phenetic analysis and DNA-DNA hybridization indicate that this bacterium represents a new species. LST adheres to a variety of surfaces, including glass, plastics, and oyster shell, and has been shown to promote the settlement of oyster larvae. 相似文献
105.
Observations of Barophilic Microbial Activity in Samples of Sediment and Intercepted Particulates from the Demerara Abyssal Plain 下载免费PDF全文
To better understand the ecological significance of pressure effects on bacteria in the abyssobenthic boundary layer, experimental suspensions of sediments and sinking particulates were prepared from samples collected in boxcore and bottom-moored sediment traps at two stations (depth, 4,470 and 4,850m) in the Demerara abyssal plain off the coast of Brazil. Replicate samples were incubated shipboard at 3°C and at both atmospheric and deep-sea pressures (440 or 480 atm [4.46 × 104 or 4.86 × 104 kPa]) following the addition of [14C]glutamic acid (<10 μg liter−1) or yeast extract (0.025%) and the antibiotic nalidixic acid (0.002%). In seven of the eight samples supplemented with isotope, a barophilic microbial response was detected, i.e., substrate incorporation and respiration were greater under in situ pressure than at 1 atm (101.3 kPa). In the remaining sample, prepared from a sediment trap warmed to 24°C before recovery, pressure was observed to inhibit substrate utilization. Total bacterial counts by epifluorescence microscopy decreased with depth in each sediment core, as did utilization of glutamic acid. Significant percentages of the total bacterial populations in cold sediment trap samples (but not the prewarmed one or any boxcore sample) were abnormally enlarged and orange fluorescing after incubation with yeast extract and nalidixic acid under deep-sea conditions. Results indicated that in the deep sea, barophilic bacteria play a predominant role in the turnover of naturally low levels of glutamic acid, and the potential for intense microbial activity upon nutrient enrichment is more likely to occur in association with recently settled particulates, especially fecal pellets, than in buried sediments. 相似文献
106.
Beadell JS Ishtiaq F Covas R Melo M Warren BH Atkinson CT Bensch S Graves GR Jhala YV Peirce MA Rahmani AR Fonseca DM Fleischer RC 《Proceedings. Biological sciences / The Royal Society》2006,273(1604):2935-2944
The introduction of avian malaria (Plasmodium relictum) to Hawaii has provided a model system for studying the influence of exotic disease on naive host populations. Little is known, however, about the origin or the genetic variation of Hawaii's malaria and traditional classification methods have confounded attempts to place the parasite within a global ecological and evolutionary context. Using fragments of the parasite mitochondrial gene cytochrome b and the nuclear gene dihydrofolate reductase-thymidylate synthase obtained from a global survey of greater than 13000 avian samples, we show that Hawaii's avian malaria, which can cause high mortality and is a major limiting factor for many species of native passerines, represents just one of the numerous lineages composing the morphological parasite species. The single parasite lineage detected in Hawaii exhibits a broad host distribution worldwide and is dominant on several other remote oceanic islands, including Bermuda and Moorea, French Polynesia. The rarity of this lineage in the continental New World and the restriction of closely related lineages to the Old World suggest limitations to the transmission of reproductively isolated parasite groups within the morphological species. 相似文献
107.
Fungal antagonists of the plant pathogen Rhizoctonia solani: selection, control efficacy and influence on the indigenous microbial community 总被引:1,自引:0,他引:1
Rita Grosch Katja Scherwinski Jana Lottmann Gabriele Berg 《Mycological Research》2006,110(12):1464-1474
A broad spectrum of fungal antagonists was evaluated as potential biocontrol agents (BCAs) against the soil-borne pathogen Rhizoctonia solani using a new combination of in vitro and in vivo assays. The in vitro characterisation of diverse parameters including the ability to parasitise mycelium and to inhibit the germination of Rhizoctonia sclerotia at different temperatures resulted in the selection of six potential fungal antagonists. These were genotypically characterised by their BOX-PCR fingerprints, and identified as Trichoderma reesei and T. viride by partial 18S rDNA sequencing. When potato sprouts were treated with Trichoderma, all isolates significantly reduced the incidence of Rhizoctonia symptoms. Evaluated under growth chamber conditions, the selected Trichoderma isolates either partly or completely controlled the dry mass loss of lettuce caused by R. solani. Furthermore, the antagonistic Trichoderma strains were active under field conditions. To analyse the effect of Trichoderma treatment on indigenous root-associated microbial communities, we performed a DNA-dependent SSCP (Single-Strand Conformation Polymorphism) analysis of 16S rDNA/ITS sequences. In this first assessment study for Trichoderma it was shown that the pathogen and the vegetation time had much more influence on the composition of the microbiota than the BCA treatment. After evaluation of all results, three Trichoderma strains originally isolated from Rhizoctonia sclerotia were selected as promising BCAs. 相似文献
108.
In this work, we used antibodies against histone H3 trimethylated at lysine 9 (H3K9m3); against histone H4 acetylated at lysines 5, 8, 12, and 16 (H4ac); and against DNA methylated at 5C cytosine (m5C) to study the presence and distribution of these markers in the genome of the isopod crustacean Asellus aquaticus. The use of these 3 antibodies to immunolabel spermatogonial metaphases yields reproducible patterns on the chromosomes of this crustacean. The X and Y chromosomes present an identical banding pattern with each of the antibodies. The heterochromatic telomeric regions and the centromeric regions are rich in H3K9m3, but depleted in m5C and H4ac. Thus, m5C does not seem to be required to stabilize the silence of these regions in this organism. 相似文献
109.
Rita Flix Soares Ana Rita Garcia Ana Raquel Monteiro Filipa Macedo Tatiana Cunha Pereira Joana Cunha Carvalho Antnio Pêgo Mnica Mariano Pedro Madeira Sara Pvoa Sofia Broco Teresa Carvalho Isabel Pazos Gabriela Sousa 《Reports of Practical Oncology and Radiotherapy》2021,26(4):563
BackgroundTriple negative breast cancer (TNBC) has the worst prognosis amongst all subtypes. Studies have shown that the achievement of pathologic complete response in the breast and axilla correlates with improved survival. The aim of this study was to identify clinical or pathological features of real-life TNBC patients with a higher risk of early relapse.Materials and methodsSingle-centre retrospective analysis of 127 women with TNBC, stage II–III, submitted to neoadjuvant treatment and surgery between January 2016 and 2020. Multivariate Cox regression analysis for disease free survival (DFS) at 2 years was performed and statistically significant variables were computed into a prognostic model for early relapse.ResultsAfter 29 months of median follow-up, 105 patients (82.7%) were alive and, in total, 38 patients (29.9%) experienced recurrence. The 2-year DFS was 73% (95% CI: 21.3–22.7). In multivariate analysis, being submitted to neoadjuvant radiotherapy [HR 2.8 (95% CI: 1.2–6.4), p = 0.017] and not achieving pathologic complete response [HR 0.3 (95% CI: 0.1–1.7), p = 0.011] were associated with higher risk of recurrence. In our prognostic model, the presence of at least one of these variables defined a subgroup of patients with a worse 2-year DFS than those without these features (59% vs. 90%, p < 0.001, respectively).ConclusionsIn this real-life non-metastatic TNBC cohort, neoadjuvant radiotherapy (performed due to insufficient clinical response to neoadjuvant chemotherapy or significant toxicity) impacted as an independent prognostic factor for relapse along with the absence of pathologic complete response identifying a subgroup of higher risk patients for early relapse that might merit a closer follow-up. 相似文献
110.
The chromate-inducible chrBACF operon from the transposable element TnOtChr confers resistance to chromium(VI) and superoxide 下载免费PDF全文
Branco R Chung AP Johnston T Gurel V Morais P Zhitkovich A 《Journal of bacteriology》2008,190(21):6996-7003
Large-scale industrial use of chromium(VI) has resulted in widespread contamination with carcinogenic chromium(VI). The abilities of microorganisms to survive in these environments and to detoxify chromate require the presence of specific resistance systems. Here we report identification of the transposon-located (TnOtChr) chromate resistance genes from the highly tolerant strain Ochrobactrum tritici 5bvl1 surviving chromate concentrations of >50 mM. The 7,189-bp-long TnOtChr of the mixed Tn21/Tn3 transposon subfamily contains a group of chrB, chrA, chrC, and chrF genes situated between divergently transcribed resolvase and transposase genes. The chrB and chrA genes, but not chrF or chrC, were essential for establishment of high resistance in chromium-sensitive O. tritici. The chr promoter was strongly induced by chromate or dichromate, but it was completely unresponsive to Cr(III), oxidants, sulfate, or other oxyanions. Plasmid reporter experiments identified ChrB as a chromate-sensing regulator of chr expression. Induction of the chr operon suppressed accumulation of cellular Cr through the activity of a chromate efflux pump encoded by chrA. Expression of chrB, chrC, or chrF in an Escherichia coli sodA sodB double mutant restored its aerobic growth in minimal medium and conferred resistance to superoxide-generating agents menadione and paraquat. Nitroblue tetrazolium staining on native gels showed that ChrC protein had superoxide dismutase activity. TnOtChr appears to represent a mobile genetic system for the distribution of the chromate-regulated resistance operon. The presence of three genes protecting against superoxide toxicity should provide an additional survival advantage to TnOtChr-containing cells in the environments with multiple redox-active contaminants. 相似文献