全文获取类型
收费全文 | 773篇 |
免费 | 105篇 |
专业分类
878篇 |
出版年
2022年 | 9篇 |
2021年 | 8篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 16篇 |
2017年 | 23篇 |
2016年 | 23篇 |
2015年 | 34篇 |
2014年 | 33篇 |
2013年 | 35篇 |
2012年 | 67篇 |
2011年 | 53篇 |
2010年 | 37篇 |
2009年 | 30篇 |
2008年 | 44篇 |
2007年 | 44篇 |
2006年 | 36篇 |
2005年 | 37篇 |
2004年 | 31篇 |
2003年 | 37篇 |
2002年 | 41篇 |
2001年 | 13篇 |
2000年 | 7篇 |
1999年 | 17篇 |
1998年 | 18篇 |
1997年 | 10篇 |
1996年 | 18篇 |
1995年 | 12篇 |
1994年 | 16篇 |
1993年 | 3篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 4篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1981年 | 14篇 |
1980年 | 4篇 |
1979年 | 7篇 |
1978年 | 5篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1971年 | 2篇 |
1969年 | 4篇 |
1967年 | 3篇 |
1966年 | 4篇 |
排序方式: 共有878条查询结果,搜索用时 0 毫秒
81.
Lazzaro A Hartmann M Blaser P Widmer F Schulin R Frey B 《FEMS microbiology ecology》2006,58(2):278-292
In this study we compared indicators of Cd bioavailability (water extracts, Lakanen extracts, free ions) and ecotoxicity in forest soils with contrasting physico-chemical characteristics. Soil samples were treated with CdCl(2) solutions (0, 0.1, 1, 10 and 100 mM) and incubated for 30 days. Microbial activity indexes (acid phosphatase, beta-glucosidase, basal respiration) and changes in bacterial community structure using terminal restriction fragment length polymorphism (T-RFLP) fingerprinting were investigated. The Cd concentrations measured ranged from 1% to 37% of the total additions in water extracts, to higher levels in Lakanen extracts. Effects of Cd were observed at bioavailable concentrations exceeding United Nations/European Economic Commission UN/ECE guidelines for total Cd in the soil solution. Basal respiration was the most affected index, while enzymatic activities showed variable responses to the Cd treatments. We also noticed that soils with pH higher than 6.7 and clay content higher than 50% showed inhibition of basal respiration but no marked shift in bacterial community structure. Soils with lower pH (pH <5.8) with less clay content (<50%) showed in addition strong changes in the bacterial community structure. Our results provide evidence for the importance of relating the effects of Cd on the soil communities to soil properties and to bioavailability. 相似文献
82.
It is often assumed that radiation-induced secondary cancer after proton therapy forms preferentially close to the distal fall-off of the spread-out Bragg peak because of an increased relative biological effectiveness (RBE) with regard to cancer induction of low-energy protons. In this study we analyze to what extent dose gradients distal to the Planning Target Volume (PTV) may, independently from the RBE, contribute to enhanced radiation carcinogenesis. The study is based on two dogs which, out of 30 dogs treated with proton therapy at the Paul Scherrer Institute (PSI), developed a secondary cancer. Both dogs were originally diagnosed and treated for a fibrosarcoma and developed an osteosarcoma 48 and almost 60 months, respectively, after radiotherapy. From the dose distributions of the initial radiotherapy for both dogs three-dimensional maps of secondary cancer complication probability (SCCP) were computed. The SCCP maps were analyzed in the regions where the dogs developed a secondary cancer. The SCCP maps showed an enhanced risk in the regions of the femur where the secondary cancers were detected, as compared to the SCCP of the total femur. Excess risk of radiation-induced cancer at the distal part of proton radiation fields can thus be explained using SCCP calculations on the basis of the physical dose distributions. Therefore, the occurrence of secondary cancer close to the distal dose gradients of proton therapy is not necessarily due to an increased RBE of low-energy protons. More extensive studies based on more patients will be necessary to further elucidate the factors influencing the development of secondary tumors. 相似文献
83.
S100 proteins form a growing subfamily of proteins related by Ca2+-binding motifs to the Efhand Ca2+-binding protein superfamily. By analyzing a human lung cancer cell line subtraction cDNA library, we have identified and characterized a new member of the human S100 family that we named S100A14 (GenBank acc. no. NM_020672). It encodes a mRNA present in several normal human tissues of epithelial origin, with the highest level of expression in colon. The full-length cDNA is 1067 nt in length, with a coding region predicting a protein of 104 amino acids that is 68% homologous to the S100A13 protein. The deduced amino acid sequence of the human S100A14 and its mouse homolog (identified as GenBank entry) contains two EF-hand Ca2+-binding domains, a myristoylation motif, a glycosylation site, and several potential protein kinase phosphorylation sites. We have mapped this gene to human chromosome 1q21, within a region where at least 15 other S100 genes are tightly clustered. A 3.2-kb genomic fragment containing the entire S100A14 was cloned and sequenced. The gene is split into four exons and three introns spanning a total of 2165 bp of genomic sequence. We examined the intracellular distribution of the epitope-tagged S100A14 protein in two human lung carcinoma cell lines and one immortalized monkey cell line. Pronounced staining was observed in the cytoplasm, suggesting an association with the plasma membrane and in the perinuclear area. We also provide evidence for heterogenic expression of S100A14 in tumors, demonstrating its overexpression in ovary, breast, and uterus tumors and underexpression in kidney, rectum, and colon tumors, a pattern suggesting distinct regulation with potentially important functions in malignant transformation. 相似文献
84.
Rüst CA Knechtle B Wirth A Knechtle P Ellenrieder B Rosemann T Lepers R 《The Chinese journal of physiology》2012,55(3):156-162
"The aim of this study was to investigate whether the characteristics of anthropometry, training or previous performance were related to an Ironman race time in recreational female Ironman triathletes. These characteristics were correlated to an Ironman race time for 53 recreational female triathletes in order to determine the predictor variables, and so be able to predict an Ironman race time for future novice triathletes. In the bi-variate analysis, no anthropometric characteristic was related to race time. The weekly cycling kilometers (r = -0.35) and hours (r = -0.32), as well as the personal best time in an Olympic distance triathlon (r = 0.49) and in a marathon (r = 0.74) were related to an Ironman race time (< 0.05). Stepwise multiple regressions showed that both the personal best time in an Olympic distance triathlon ( P = 0.0453) and in a marathon (P = 0.0030) were the best predictors for the Ironman race time (n = 28, r2 = 0.53). The race time in an Ironman triathlon might be partially predicted by the following equation (r2 = 0.53, n = 28): Race time (min) = 186.3 + 1.595 × (personal best time in an Olympic distance triathlon, min) + 1.318 × (personal best time in a marathon, min) for recreational female Ironman triathletes." 相似文献
85.
Mark Bauer Andrea Chicca Marco Tamborrini David Eisen Raissa Lerner Beat Lutz Oliver Poetz Gerd Pluschke Jürg Gertsch 《The Journal of biological chemistry》2012,287(44):36944-36967
The α-hemoglobin-derived dodecapeptide RVD-hemopressin (RVDPVNFKLLSH) has been proposed to be an endogenous agonist for the cannabinoid receptor type 1 (CB1). To study this peptide, we have raised mAbs against its C-terminal part. Using an immunoaffinity mass spectrometry approach, a whole family of N-terminally extended peptides in addition to RVD-Hpα were identified in rodent brain extracts and human and mouse plasma. We designated these peptides Pepcan-12 (RVDPVNFKLLSH) to Pepcan-23 (SALSDLHAHKLRVDPVNFKLLSH), referring to peptide length. The most abundant Pepcans found in the brain were tested for CB1 receptor binding. In the classical radioligand displacement assay, Pepcan-12 was the most efficacious ligand but only partially displaced both [3H]CP55,940 and [3H]WIN55,212-2. The data were fitted with the allosteric ternary complex model, revealing a cooperativity factor value α < 1, thus indicating a negative allosteric modulation. Dissociation kinetic studies of [3H]CP55,940 in the absence and presence of Pepcan-12 confirmed these results by showing increased dissociation rate constants induced by Pepcan-12. A fluorescently labeled Pepcan-12 analog was synthesized to investigate the binding to CB1 receptors. Competition binding studies revealed Ki values of several Pepcans in the nanomolar range. Accordingly, using competitive ELISA, we found low nanomolar concentrations of Pepcans in human plasma and ∼100 pmol/g in mouse brain. Surprisingly, Pepcan-12 exhibited potent negative allosteric modulation of the orthosteric agonist-induced cAMP accumulation, [35S]GTPγS binding, and CB1 receptor internalization. Pepcans are the first endogenous allosteric modulators identified for CB1 receptors. Given their abundance in the brain, Pepcans could play an important physiological role in modulating endocannabinoid signaling. 相似文献
86.
87.
Régis Céréghino Beat Oertli Marcello Bazzanti Cristina Coccia Arthur Compin Jeremy Biggs Nicolas Bressi Patrick Grillas Andrew Hull Thomas Kalettka Olivier Scher 《Hydrobiologia》2012,689(1):51-61
Whilst biological traits of river macroinvertebrates show unimodal responses to geographic changes in habitat conditions in Europe, we still do not know whether spatial turnover of species result in distinct combinations of biological traits for pond macroinvertebrates. Here, we used data on the occurrence of 204 macroinvertebrate taxa in 120 ponds from four biogeographic regions of Europe, to compare their biological traits. The Mediterranean, Atlantic, Alpine, and Continental regions have specific climate, vegetation and geology. Only two taxa were exclusively found in the Alpine and Continental regions, while 28 and 34 taxa were exclusively recorded in the Atlantic and Mediterranean regions, respectively. Invertebrates in the Mediterranean region allocated much energy to reproduction and resistance forms. Most Mediterranean invertebrate species had narrow thermal ranges. In Continental areas, invertebrates allocated lesser energy to reproduction and dispersal, and organisms were short lived with high diversity of feeding groups. These characteristics suggest higher resilience. The main difference between ponds in the Alpine and Atlantic regions was their elevation. Alpine conditions necessitate specific adaptations related to rapid temperature fluctuations, and low nutrient concentrations. Even if our samples did not cover the full range of pond conditions across Europe, our analyses suggest that changes in community composition have important impacts on pond ecosystem functions. Consistent information on a larger set of ponds across Europe would be much needed, but their low accessibility (unpublished data and/or not disclosed by authors) remains problematic. There is still, therefore, a pressing need for the incorporation of high quality data sets into a standardized database so that they can be further analyzed in an integrated European-wide manner. 相似文献
88.
Nielsen AB Székely K Gath J Ernst M Nielsen NC Meier BH 《Journal of biomolecular NMR》2012,52(4):283-288
We present a scheme that allows the simultaneous detection of PAR and PAIN correlation spectra in a single two-dimensional
experiment. For both spectra, we obtain almost the same signal-to-noise ratio as if a PAR or PAIN spectrum is recorded separately,
which in turn implies that one of the spectra may be considered additional information for free. The experiment is based on
the observation that in a PAIN experiment, the PAR condition is always also fulfilled. The performance is demonstrated experimentally
using uniformly 13C,15N-labeled samples of N–f–MLF–OH and ubiquitin. 相似文献
89.
Chromatin is extensively chemically modified and thereby acts as a dynamic signaling platform controlling gene function. Chromatin regulation is integral to cell differentiation, lineage commitment and organism development, whereas chromatin dysregulation can lead to age-related and neurodegenerative disorders as well as cancer. Investigating chromatin biology presents a unique challenge, as the issue spans many disciplines, including cell and systems biology, biochemistry and molecular biophysics. In recent years, the application of chemical biology methods for investigating chromatin processes has gained considerable traction. Indeed, chemical biologists now have at their disposal powerful chemical tools that allow chromatin biology to be scrutinized at the level of the cell all the way down to the single chromatin fiber. Here we present recent examples of how this rapidly expanding palette of chemical tools is being used to paint a detailed picture of chromatin function in organism development and disease. 相似文献
90.
Dervillez X Gottimukkala C Kabbara KW Nguyen C Badakhshan T Kim SM Nesburn AB Wechsler SL Benmohamed L 《Future virology》2012,7(4):371-378
Considering the limited success of the recent herpes clinical vaccine trial [1], new vaccine strategies are needed. Infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) in the majority of men and women are usually asymptomatic and results in lifelong viral latency in neurons of sensory ganglia (SG). However, in a minority of men and women HSV spontaneous reactivation can cause recurrent disease (i.e., symptomatic individuals). Our recent findings show that T cells from symptomatic and asymptomatic men and women (i.e. those with and without recurrences, respectively) recognize different herpes epitopes. This finding breaks new ground and opens new doors to assess a new vaccine strategy: mucosal immunization with HSV-1 & HSV-2 epitopes that induce strong in vitro CD4 and CD8 T cell responses from PBMC derived from asymptomatic men and women (designated here as "asymptomatic" protective epitopes") could boost local and systemic "natural" protective immunity, induced by wild-type infection. Here we highlight the rationale and the future of our emerging "asymptomatic" T cell epitope-based mucosal vaccine strategy to decrease recurrent herpetic disease. 相似文献