全文获取类型
收费全文 | 3556篇 |
免费 | 309篇 |
国内免费 | 2篇 |
专业分类
3867篇 |
出版年
2023年 | 17篇 |
2022年 | 27篇 |
2021年 | 62篇 |
2020年 | 33篇 |
2019年 | 50篇 |
2018年 | 93篇 |
2017年 | 79篇 |
2016年 | 104篇 |
2015年 | 168篇 |
2014年 | 207篇 |
2013年 | 269篇 |
2012年 | 305篇 |
2011年 | 262篇 |
2010年 | 174篇 |
2009年 | 161篇 |
2008年 | 226篇 |
2007年 | 209篇 |
2006年 | 220篇 |
2005年 | 199篇 |
2004年 | 205篇 |
2003年 | 192篇 |
2002年 | 175篇 |
2001年 | 39篇 |
2000年 | 24篇 |
1999年 | 36篇 |
1998年 | 39篇 |
1997年 | 26篇 |
1996年 | 29篇 |
1995年 | 32篇 |
1994年 | 21篇 |
1993年 | 22篇 |
1992年 | 12篇 |
1991年 | 14篇 |
1990年 | 14篇 |
1989年 | 21篇 |
1988年 | 12篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1981年 | 6篇 |
1980年 | 8篇 |
1979年 | 4篇 |
1978年 | 8篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1974年 | 3篇 |
1960年 | 3篇 |
排序方式: 共有3867条查询结果,搜索用时 15 毫秒
101.
102.
Tarabbo M Lapa D Castilletti C Tommaselli P Guarducci R Lucà G Emanuele A Zaccaria O La Gioia VF Girardi E Capobianchi MR Ippolito G 《PloS one》2011,6(1):e15933
Background
Clinical surveillance may have underestimated the real extent of the spread of the new strain of influenza A/H1N1, which surfaced in April 2009 originating the first influenza pandemic of the 21st century. Here we report a serological investigation on an influenza A/H1N1pdm outbreak in an Italian military ship while cruising in the Mediterranean Sea (May 24-September 6, 2009).Methods
The contemporary presence of HAI and CF antibodies was used to retrospectively estimate the extent of influenza A/H1N1pdm spread across the crew members (median age: 29 years).Findings
During the cruise, 2 crew members fulfilled the surveillance case definition for influenza, but only one was laboratory confirmed by influenza A/H1N1pdm-specific RT-PCR; 52 reported acute respiratory illness (ARI) episodes, and 183 reported no ARI episodes. Overall, among the 211 crew member for whom a valid serological result was available, 39.3% tested seropositive for influenza A/H1N1pdm. The proportion of seropositives was significantly associated with more crowded living quarters and tended to be higher in those aged <40 and in those reporting ARI or suspected/confirmed influenza A/H1N1pdm compared to the asymptomatic individuals. No association was found with previous seasonal influenza vaccination.Conclusions
These findings underline the risk for rapid spread of novel strains of influenza A in confined environment, such as military ships, where crowding, rigorous working environment, physiologic stress occur. The high proportion of asymptomatic infections in this ship-borne outbreak supports the concept that serological surveillance in such semi-closed communities is essential to appreciate the real extent of influenza A/H1N1pdm spread and can constitute, since the early stage of a pandemic, an useful model to predict the public health impact of pandemic influenza and to establish proportionate and effective countermeasures. 相似文献103.
Eveline Dirinck Philippe G. Jorens Adrian Covaci Tinne Geens Laurence Roosens Hugo Neels Ilse Mertens Luc van Gaal 《Obesity (Silver Spring, Md.)》2011,19(4):709-714
Persistent organic pollutants (POPs) are endocrine‐disrupting chemicals associated with the development of the metabolic syndrome and type 2 diabetes. In humans, little is known about their role in the potential origin of obesity. This study aims to assess the associations between serum levels of POPs and the prevalence of obesity in a cohort of obese and lean adult men and women. POP serum samples were investigated cross‐sectionally in 98 obese and 47 lean participants, aged ≥18 years. Serum samples were analyzed for the presence of polychlorinated biphenyl (PCB) congeners 153, 138, 180, and 170 and for the organochlorine pesticides, dichloro‐diphenyl‐dichloroethylene (pp‐DDE), and β‐hexachlorocyclohexane (βHCH). We established a significant negative correlation between BMI, waist, fat mass percentage, total and subcutaneous abdominal adipose tissue, and serum levels of PCB 153, 180, 170, and the sumPCBs. For βHCH, we demonstrated a positive correlation with BMI, waist, fat mass percentage, and total and subcutaneous abdominal adipose tissue. PCBs 180, 170, and the sum of PCBs correlated significantly negative with homeostasis model assessment for insulin resistance (HOMAIR). βHCH correlated significantly positively with HOMAIR. A strong correlation was established between all POP serum levels and age. We established a positive relationship between high serum levels of βHCH and BMI and HOMAIR, whereas serum PCB levels were inversely correlated with BMI and HOMAIR. Combined, these results suggest that the diabetogenic effect of low‐dose exposure to POPs might be more complicated than a simple obesogenic effect. 相似文献
104.
Luc Demange Fatma Nait Abdellah Olivier Lozach Yoan Ferandin Nohad Gresh Laurent Meijer Hervé Galons 《Bioorganic & medicinal chemistry letters》2013,23(1):125-131
Cyclin dependent kinase 5 (CDK5) is a serine/threonine kinase belonging to the cyclin dependent kinase (CDK) family. CDK5 is involved in numerous neuronal diseases (including Alzheimer’s or Parkinson’s diseases, stroke, traumatic brain injury), pain signaling and cell migration. In the present Letter, we describe syntheses and biological evaluations of new 2,6,9-trisubstituted purines, structurally related to roscovitine, a promising CDK inhibitor currently in clinical trials (CDK1/Cyclin B, IC50 = 350 nM; CDK5/p25, IC50 = 200 nM). These new molecules were synthesized using an original Buchwald–Hartwig catalytic procedure; several compounds (3j, 3k, 3l, 3e, 4k, 6b, 6c) displayed potent kinase inhibitory potencies against CDK5 (IC50 values ranging from 17 to 50 nM) and showed significant cell death inducing activities (IC50 values ranging from 2 to 9 μM on SH-SY5Y). The docking of the inhibitors into the ATP binding domain of the CDK5 catalytic site highlighted the discriminatory effect of a hydrogen bond involving the CDK5 Lys-89. In addition, the calculated final energy balances for complexation measured for several inhibitors is consistent with the ranking of the IC50 values. Lastly, we observed that several compounds exhibit submicromolar activities against DYRK1A (dual specificity, tyrosine phosphorylation regulated kinase 1A), a kinase involved in Down syndrome and Alzheimer’s disease (3g, 3h, 4m; IC50 values ranging from 300 to 400 nM). 相似文献
105.
Marijke De Saint-Hubert Felix M. Mottaghy Kathleen Vunckx Johan Nuyts Humphrey Fonge Kristof Prinsen Sigrid Stroobants Luc Mortelmans Niko Deckers Leo Hofstra Chris P.M. Reutelingsperger Alfons Verbruggen Dirk Rattat 《Bioorganic & medicinal chemistry》2010,18(3):1356-1363
In this study ‘second generation’ AnxV was specifically labeled with 99mTc in three different ways outside the binding region of the protein to obtain an improved target-to-background activity ratio. The compounds were tested in vitro and in vivo in normal mice and in a model of hepatic apoptosis (anti-Fas mAb). The apoptosis binding was most prominent for the HIS-tagged ‘second generation’ AnxV labeled with 99mTc(CO)3 in comparison to 99mTc-HYNIC-cys-AnxV and 99mTc(CO)3-DTPA-cys-AnxV. 相似文献
106.
107.
Thieno[3,4‐c]Pyrrole‐4,6‐Dione‐Based Polymer Acceptors for High Open‐Circuit Voltage All‐Polymer Solar Cells 下载免费PDF全文
Shengjian Liu Xin Song Simil Thomas Zhipeng Kan Federico Cruciani Frédéric Laquai Jean‐Luc Bredas Pierre M. Beaujuge 《Liver Transplantation》2017,7(15)
While polymer acceptors are promising fullerene alternatives in the fabrication of efficient bulk heterojunction (BHJ) solar cells, the range of efficient material systems relevant to the “all‐polymer” BHJ concept remains narrow, and currently limits the perspectives to meet the 10% efficiency threshold in all‐polymer solar cells. This report examines two polymer acceptor analogs composed of thieno[3,4‐c ]pyrrole‐4,6‐dione (TPD) and 3,4‐difluorothiophene ([2F]T) motifs, and their BHJ solar cell performance pattern with a low‐bandgap polymer donor commonly used with fullerenes (PBDT‐TS1; taken as a model system). In this material set, the introduction of a third electron‐deficient motif, namely 2,1,3‐benzothiadiazole (BT), is shown to (i) significantly narrow the optical gap (E opt) of the corresponding polymer (by ≈0.2 eV) and (ii) improve the electron mobility of the polymer by over two orders of magnitude in BHJ solar cells. In turn, the narrow‐gap P2TPDBT[2F]T analog (E opt = 1.7 eV) used as fullerene alternative yields high open‐circuit voltages (V OC) of ≈1.0 V, notable short‐circuit current values (J SC) of ≈11.0 mA cm−2, and power conversion efficiencies (PCEs) nearing 5% in all‐polymer BHJ solar cells. P2TPDBT[2F]T paves the way to a new, promising class of polymer acceptor candidates. 相似文献
108.
Darwin J. Prockop Malcolm Brenner Willem E. Fibbe Edwin Horwitz Katarina Le Blanc Donald G. Phinney Paul J. Simmons Luc Sensebe Armand Keating 《Cytotherapy》2010,12(5):576-578
We address the issue of the potential for malignant transformation of cultured mesenchymal stromal cells (MSC) commonly used in clinical cell-therapy protocols and describe the culture conditions under which tumorigenesis is likely to be an extremely uncommon event. 相似文献
109.
Jeong Y Xie Y Lee W Bookout AL Girard L Raso G Behrens C Wistuba II Gadzar AF Minna JD Mangelsdorf DJ 《Molecular endocrinology (Baltimore, Md.)》2012,26(8):1443-1454
Lung cancer is the leading cause of cancer-related death. Despite a number of studies that have provided prognostic biomarkers for lung cancer, a paucity of reliable markers and therapeutic targets exist to diagnose and treat this aggressive disease. In this study we investigated the potential of nuclear receptors (NRs), many of which are well-established drug targets, as therapeutic markers in lung cancer. Using quantitative real-time PCR, we analyzed the expression of the 48 members of the NR superfamily in a human panel of 55 normal and lung cancer cell lines. Unsupervised cluster analysis of the NR expression profile segregated normal from tumor cell lines and grouped lung cancers according to type (i.e. small vs. non-small cell lung cancers). Moreover, we found that the NR signature was 79% accurate in diagnosing lung cancer incidence in smokers (n = 129). Finally, the evaluation of a subset of NRs (androgen receptor, estrogen receptor, vitamin D receptor, and peroxisome proliferator-activated receptor-γ) demonstrated the therapeutic potential of using NR expression to predict ligand-dependent growth responses in individual lung cancer cells. Preclinical evaluation of one of these receptors (peroxisome proliferator activated receptor-γ) in mouse xenografts confirmed that ligand-dependent inhibitory growth responses in lung cancer can be predicted based on a tumor's receptor expression status. Taken together, this study establishes NRs as theragnostic markers for predicting lung cancer incidence and further strengthens their potential as therapeutic targets for individualized treatment. 相似文献
110.
Emerging high-throughput approaches to analyze bioremediation of sites contaminated with hazardous and/or recalcitrant wastes 总被引:1,自引:0,他引:1
Sustainable development requires the promotion of environmental management and a constant search for new technologies to treat a wide range of aquatic and terrestrial habitats contaminated by increasing anthropogenic activities. Bioremediation, i.e. the elimination of natural or xenobiotic pollutants by living organisms, is an environmentally friendly and cost-effective alternative to physico-chemical cleanup options. However, the strategy and outcome of bioremediation in open systems or confined environments depend on a variety of physico-chemical and biological factors that need to be assessed and monitored. In particular, microorganisms are key players in bioremediation applications, yet their catabolic potential and their dynamics in situ remain poorly characterized. To perform a comprehensive assessment of the biodegradative potential of a contaminated site and efficiently monitor changes in the structure and activities of microbial communities involved in bioremediation processes, sensitive, fast and large-scale methods are needed. Over the last few years, the scientific literature has revealed the progressive emergence of genomic high-throughput technologies in environmental microbiology and biotechnology. In this review, we discuss various high--throughput techniques and their possible--or already demonstrated-application to assess biotreatment of contaminated environments. 相似文献