全文获取类型
收费全文 | 1110篇 |
免费 | 83篇 |
国内免费 | 6篇 |
专业分类
1199篇 |
出版年
2021年 | 17篇 |
2020年 | 5篇 |
2019年 | 7篇 |
2017年 | 15篇 |
2016年 | 14篇 |
2015年 | 42篇 |
2014年 | 59篇 |
2013年 | 59篇 |
2012年 | 70篇 |
2011年 | 59篇 |
2010年 | 42篇 |
2009年 | 35篇 |
2008年 | 54篇 |
2007年 | 62篇 |
2006年 | 46篇 |
2005年 | 33篇 |
2004年 | 52篇 |
2003年 | 45篇 |
2002年 | 44篇 |
2001年 | 17篇 |
2000年 | 19篇 |
1999年 | 27篇 |
1998年 | 18篇 |
1997年 | 26篇 |
1996年 | 18篇 |
1995年 | 15篇 |
1994年 | 11篇 |
1993年 | 14篇 |
1992年 | 24篇 |
1991年 | 21篇 |
1990年 | 13篇 |
1989年 | 17篇 |
1988年 | 12篇 |
1987年 | 12篇 |
1986年 | 20篇 |
1985年 | 14篇 |
1984年 | 9篇 |
1983年 | 10篇 |
1982年 | 7篇 |
1981年 | 7篇 |
1980年 | 8篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1976年 | 11篇 |
1973年 | 10篇 |
1972年 | 6篇 |
1970年 | 6篇 |
1969年 | 4篇 |
1968年 | 4篇 |
排序方式: 共有1199条查询结果,搜索用时 15 毫秒
61.
Christine Breynaert Tom Dresselaers Clémentine Perrier Ingrid Arijs Jonathan Cremer Leentje Van Lommel Kristel Van Steen Marc Ferrante Frans Schuit Séverine Vermeire Paul Rutgeerts Uwe Himmelreich Jan L. Ceuppens Karel Geboes Gert Van Assche 《PloS one》2013,8(7)
Introduction
Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS) ingestion, to mimic the relapsing nature of the human disease.Materials and Methods
C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total). Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T 2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis.Results
Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn’s colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS.Conclusions
Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn’s disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of inflammation and fibrosis. 相似文献62.
Background
The number of retracted scientific publications has risen sharply, but it is unclear whether this reflects an increase in publication of flawed articles or an increase in the rate at which flawed articles are withdrawn.Methods and Findings
We examined the interval between publication and retraction for 2,047 retracted articles indexed in PubMed. Time-to-retraction (from publication of article to publication of retraction) averaged 32.91 months. Among 714 retracted articles published in or before 2002, retraction required 49.82 months; among 1,333 retracted articles published after 2002, retraction required 23.82 months (p<0.0001). This suggests that journals are retracting papers more quickly than in the past, although recent articles requiring retraction may not have been recognized yet. To test the hypothesis that time-to-retraction is shorter for articles that receive careful scrutiny, time-to-retraction was correlated with journal impact factor (IF). Time-to-retraction was significantly shorter for high-IF journals, but only ∼1% of the variance in time-to-retraction was explained by increased scrutiny. The first article retracted for plagiarism was published in 1979 and the first for duplicate publication in 1990, showing that articles are now retracted for reasons not cited in the past. The proportional impact of authors with multiple retractions was greater in 1972–1992 than in the current era (p<0.001). From 1972–1992, 46.0% of retracted papers were written by authors with a single retraction; from 1993 to 2012, 63.1% of retracted papers were written by single-retraction authors (p<0.001).Conclusions
The increase in retracted articles appears to reflect changes in the behavior of both authors and institutions. Lower barriers to publication of flawed articles are seen in the increase in number and proportion of retractions by authors with a single retraction. Lower barriers to retraction are apparent in an increase in retraction for “new” offenses such as plagiarism and a decrease in the time-to-retraction of flawed work. 相似文献63.
Glucose‐based microbial production of the hormone melatonin in yeast Saccharomyces cerevisiae 下载免费PDF全文
Susanne M. Germann Simo A. Baallal Jacobsen Konstantin Schneider Scott J. Harrison Niels B. Jensen Xiao Chen Steen G. Stahlhut Irina Borodina Hao Luo Jiangfeng Zhu Jérôme Maury Jochen Forster 《Biotechnology journal》2016,11(5):717-724
Melatonin is a natural mammalian hormone that plays an important role in regulating the circadian cycle in humans. It is a clinically effective drug exhibiting positive effects as a sleep aid and a powerful antioxidant used as a dietary supplement. Commercial melatonin production is predominantly performed by complex chemical synthesis. In this study, we demonstrate microbial production of melatonin and related compounds, such as serotonin and N‐acetylserotonin. We generated Saccharomyces cerevisiae strains that comprise heterologous genes encoding one or more variants of an L‐tryptophan hydroxylase, a 5‐hydroxy‐L‐tryptophan decarboxylase, a serotonin acetyltransferase, an acetylserotonin O‐methyltransferase, and means for providing the cofactor tetrahydrobiopterin via heterologous biosynthesis and recycling pathways. We thereby achieved de novo melatonin biosynthesis from glucose. We furthermore accomplished increased product titers by altering expression levels of selected pathway enzymes and boosting co‐factor supply. The final yeast strain produced melatonin at a titer of 14.50 ± 0.57 mg L?1 in a 76h fermentation using simulated fed‐batch medium with glucose as sole carbon source. Our study lays the basis for further developing a yeast cell factory for biological production of melatonin. 相似文献
64.
Skals Marianne Greve Anne-Sofie Fagerberg Steen K. Johnsen Nanna Christensen Mette G. Praetorius Helle A. 《Purinergic signalling》2019,15(2):265-276
Purinergic Signalling - Urosepsis is a severe condition often caused by Escherichia coli that spontaneously have ascended the urinary tract to the kidneys causing pyelonephritis and potentially... 相似文献
65.
Kirkland RM Patterson DC Keady TW Moss BW Steen RW 《Animal : an international journal of animal bioscience》2007,1(10):1506-1514
There is a paucity of data on the beef production potential of Norwegian Red (NOR) compared with 'modern' Holstein-Friesian (HF) cattle. The present study used a total of 64 bulls in a 2 × 2 factorial design study encompassing two breeds (HF and NOR) and two slaughter ages (485; E, and 610; L, days). The mean initial age and live weight of the HF bulls were 179 (s.d. 47.1) days and 203 (s.d. 64.0) kg, while the corresponding data for the NOR bulls were 176 (s.d. 39.7) days and 185 (s.d. 63.6) kg, respectively. Bulls were offered a 50 : 50 mixture (dry matter (DM) basis) of grass silage and concentrates. No breed × slaughter group interactions were recorded for any parameters evaluated (P > 0.05). HF bulls had higher (P < 0.001) DM intake and poorer (P < 0.01) efficiency of conversion of food to carcass gain than NOR bulls. HF bulls tended (P = 0.07) to have a higher rate of live-weight gain and were heavier (P < 0.001) at slaughter than NOR bulls, though both carcass weight and rate of carcass gain did not differ between the breeds (P > 0.05). NOR bulls had higher (P < 0.001) dressing proportion and carcass conformation score than HF bulls, while breed of bull had no influence (P > 0.05) on carcass fat classification, depth of subcutaneous fat, marbling score or on the weight of fat in the internal depots. Daily food intakes did not differ (P > 0.05) across the two slaughter age groups, though efficiency of conversion of food to carcass gain was poorer (P < 0.05) in the L compared with E bulls. Rate of live-weight gain was lower (P < 0.01) for L bulls, although rate of carcass gain did not differ (P > 0.05) between the E and L bulls. Increasing age at slaughter increased (P < 0.01 or greater) dressing proportion, carcass fat class, depth of subcutaneous fat, marbling score and internal fat depots, but had no effect (P > 0.05) on the carcass conformation score. Instrumental measures of meat quality indicated that meat from NOR bulls was tougher (P < 0.01) than meat from HF bulls, while delaying slaughter increased (P < 0.001) a* and C*ab, and decreased (P < 0.01) h0, indicating improved redness. It is concluded that NOR bulls have higher food efficiency and produce more highly conformed carcasses than HF bulls, but HF bulls produce more tender meat. 相似文献
66.
Grazing by large herbivores may negatively affect bird populations. This is of great conservation concern in areas with intensive sheep grazing. Sheep management varies substantially between regions, but no study has been performed in less intensively grazed systems. In a fully replicated, landscape scale experiment with three levels of sheep grazing, we tested whether the abundance and diversity of an assemblage of mountain birds were negatively affected by grazing or if grazing facilitated the bird assemblage. Density of birds was higher at high sheep density compared with low sheep density or no sheep by the fourth grazing season, while there was no clear effect on bird diversity. Thus, agricultural traditions and land use politics determining sheep density may change the density of avifauna in either positive or negative directions. 相似文献
67.
Park Soomin Steen Collin J. Fischer Alexandra L. Fleming Graham R. 《Photosynthesis research》2019,141(3):367-376
Photosynthesis Research - Although the importance of nonphotochemical quenching (NPQ) on photosynthetic biomass production and crop yields is well established, the in vivo operation of the... 相似文献
68.
O B Tysnes V M Steen G M Aarbakke H Holmsen 《The International journal of biochemistry》1991,23(3):305-310
1. Gel-filtered human platelets prelabeled with [32P]Pi or [3H]glycerol were exposed to 0-0.3 U/ml of thrombin and analyzed for radioactivities and masses in the phosphoinositides, inositol trisphosphates (IP3), phosphatidic acid (PA) and diacylglycerol (DAG) at 15 and 180 sec of stimulation. 2. At thrombin concentrations below 0.1 U/ml, PA and IP3 accumulated in equimolar amounts. 3. The production and disappearance of the metabolites of the polyphosphoinositide cycle was balanced during 180 sec of stimulation with 0.03-0.1 U/ml of thrombin. 4. Under these conditions no increase in [3H]DAG or [3H]monoacylglycerol could be detected. 5. The data indicate that all DAG is converted to PA and support our conclusion that phosphatidylinositol 4,5-bisphosphate represents the major source for production of DAG upon stimulation of human platelets with low concentrations of thrombin. 相似文献
69.
Steen IH Madern D Karlström M Lien T Ladenstein R Birkeland NK 《The Journal of biological chemistry》2001,276(47):43924-43931
With the aim of gaining insight into the molecular and phylogenetic relationships of isocitrate dehydrogenase (IDH) from hyperthermophiles, we carried out a comparative study of putative IDHs identified in the genomes of the eubacterium Thermotoga maritima and the archaea Aeropyrum pernix and Pyrococcus furiosus. An optimum for activity at 90 degrees C or above was found for each IDH. PfIDH and ApIDH were the most thermostable with a melting temperature of 103.7 and 109.9 degrees C, respectively, compared with 98.3 and 98.5 degrees C for TmIDH and AfIDH, respectively. Analytical ultracentrifugation revealed a tetrameric oligomeric state for TmIDH and a homodimeric state for ApIDH and PfIDH. TmIDH and ApIDH were NADP-dependent (K(m)((NADP)) of 55.2 and 44.4 microm, respectively) whereas PfIDH was NAD-dependent (K(m)((NAD)) of 68.3 microm). These data document that TmIDH represents a novel tetrameric NADP-dependent form of IDH and that PfIDH is a homodimeric NAD-dependent IDH not previously found among the archaea. The homodimeric NADP-IDH present in A. pernix is the most common form of IDH known so far. The evolutionary relationships of ApIDH, PfIDH, and TmIDH with all of the available amino acid sequences of di- and multimeric IDHs are described and discussed. 相似文献
70.
Patrick ME Christiansen LE Wainø M Ethelberg S Madsen H Wegener HC 《Applied and environmental microbiology》2004,70(12):7474-7480
Campylobacter infections are increasing and pose a serious public health problem in Denmark. Infections in humans and broiler flocks show similar seasonality, suggesting that climate may play a role in infection. We examined the effects of temperature, precipitation, relative humidity, and hours of sunlight on Campylobacter incidence in humans and broiler flocks by using lag dependence functions, locally fitted linear models, and cross validation methods. For humans, the best model included average temperature and sunlight 4 weeks prior to infection; the maximum temperature lagged at 4 weeks was the best single predictor. For broilers, the average and maximum temperatures 3 weeks prior to slaughter gave the best estimate; the average temperature lagged at 3 weeks was the best single predictor. The combined effects of temperature and sunlight or the combined effects of temperature and relative humidity predicted the incidence in humans equally well. For broiler flock incidence these factors explained considerably less. Future research should focus on elements within the broiler environment that may be affected by climate, as well as the interaction of microclimatic factors on and around broiler farms. There is a need to quantify the contribution of broilers as a source of campylobacteriosis in humans and to further examine the effect of temperature on human incidence after this contribution is accounted for. Investigations should be conducted into food consumption and preparation practices and poultry sales that may vary by season. 相似文献