全文获取类型
收费全文 | 782篇 |
免费 | 107篇 |
国内免费 | 2篇 |
专业分类
891篇 |
出版年
2022年 | 8篇 |
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 14篇 |
2018年 | 14篇 |
2017年 | 17篇 |
2016年 | 19篇 |
2015年 | 37篇 |
2014年 | 36篇 |
2013年 | 30篇 |
2012年 | 65篇 |
2011年 | 53篇 |
2010年 | 38篇 |
2009年 | 35篇 |
2008年 | 43篇 |
2007年 | 45篇 |
2006年 | 43篇 |
2005年 | 55篇 |
2004年 | 61篇 |
2003年 | 45篇 |
2002年 | 38篇 |
2001年 | 8篇 |
2000年 | 9篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 9篇 |
1995年 | 5篇 |
1994年 | 11篇 |
1993年 | 9篇 |
1992年 | 12篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 13篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 9篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 7篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1961年 | 2篇 |
排序方式: 共有891条查询结果,搜索用时 0 毫秒
51.
The genus Tribolium Desv. consists of nine species, i.e., T. utriculosum (Nees) Renv., T. ciliare (Stapf) Renv., T. echinatum (Thunb.) Desv., T. hispidum (Thunb.) Desv., T. acutiflorum (Nees) Renv., T. obliterum sensu Davidse, T. glomeratum sensu Davidse, T. uniolae (L.f.) Renv., and T. brachystachyum (Nees) Renv. The genus has a basic chromosome number of 6, and from diploid to hexaploid specimens have been examined. Precocious segregation of metaphase I bivalents were observed in four species. Multivalent formation results in unequal chromosome segregation during anaphase I, and several cells with an 11–13 chromosome distribution have been observed. The presence of univalents and anaphase I bridges in all T. brachystachyum specimens suggests a hybrid origin for the species. B-chromosomes were present in specimens from four species. The B-chromosomes are similar to the euchromosomes with the exception that they do not participate in meiosis. The B-chromosomes have a possible isochromosome origin. The cytogenetic evidence presented supports the combination of Plagiochloa and Lasiochloa into Tribolium and indicates that the genus is closely related to Urochlaena, whereas it is not closely related to Prionanthium. 相似文献
52.
Disorganization of cortical microtubules stimulates tangential expansion and reduces the uniformity of cellulose microfibril alignment among cells in the root of Arabidopsis 下载免费PDF全文
To test the role of cortical microtubules in aligning cellulose microfibrils and controlling anisotropic expansion, we exposed Arabidopsis thaliana roots to moderate levels of the microtubule inhibitor, oryzalin. After 2 d of treatment, roots grow at approximately steady state. At that time, the spatial profiles of relative expansion rate in length and diameter were quantified, and roots were cryofixed, freeze-substituted, embedded in plastic, and sectioned. The angular distribution of microtubules as a function of distance from the tip was quantified from antitubulin immunofluorescence images. In alternate sections, the overall amount of alignment among microfibrils and their mean orientation as a function of position was quantified with polarized-light microscopy. The spatial profiles of relative expansion show that the drug affects relative elongation and tangential expansion rates independently. The microtubule distributions averaged to transverse in the growth zone for all treatments, but on oryzalin the distributions became broad, indicating poorly organized arrays. At a subcellular scale, cellulose microfibrils in oryzalin-treated roots were as well aligned as in controls; however, the mean alignment direction, while consistently transverse in the controls, was increasingly variable with oryzalin concentration, meaning that microfibril orientation in one location tended to differ from that of a neighboring location. This conclusion was confirmed by direct observations of microfibrils with field-emission scanning electron microscopy. Taken together, these results suggest that cortical microtubules ensure microfibrils are aligned consistently across the organ, thereby endowing the organ with a uniform mechanical structure. 相似文献
53.
Thomas?H.?S.?van?KempenEmail author Gerrit?W.?M.?Peters Frans?N.?van de?Vosse 《Biomechanics and modeling in mechanobiology》2015,14(5):995-1006
Blood clot formation is important to prevent blood loss in case of a vascular injury but disastrous when it occludes the vessel. As the mechanical properties of the clot are reported to be related to many diseases, it is important to have a good understanding of their characteristics. In this study, a constitutive model is presented that describes the nonlinear viscoelastic properties of the fibrin network, the main structural component of blood clots. The model is developed using results of experiments in which the fibrin network is subjected to a large amplitude oscillatory shear (LAOS) deformation. The results show three dominating nonlinear features: softening over multiple deformation cycles, strain stiffening and increasing viscous dissipation during a deformation cycle. These features are incorporated in a constitutive model based on the Kelvin–Voigt model. A network state parameter is introduced that takes into account the influence of the deformation history of the network. Furthermore, in the period following the LAOS deformation, the stiffness of the networks increases which is also incorporated in the model. The influence of cross-links created by factor XIII is investigated by comparing fibrin networks that have polymerized for 1 and 2 h. A sensitivity analysis provides insights into the influence of the eight fit parameters. The model developed is able to describe the rich, time-dependent, nonlinear behavior of the fibrin network. The model is relatively simple which makes it suitable for computational simulations of blood clot formation and is general enough to be used for other materials showing similar behavior. 相似文献
54.
Jakob Nikolas Kather Cleo-Aron Weis Alexander Marx Alexander K. Schuster Lothar R. Schad Frank Gerrit Z?llner 《PloS one》2015,10(12)
Background
Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions.Methods and Results
In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin—3,3’-Diaminobenzidine (DAB) images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images.Validation
To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images.Context
Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics. 相似文献55.
56.
Meng-Hsin Phoebe Lee Sean M. Caffrey Johanna K. Voordouw Gerrit Voordouw 《Applied microbiology and biotechnology》2010,87(3):1109-1118
Although sulfate-reducing bacteria (SRB), such as Desulfovibrio vulgaris Hildenborough (DvH) are often eradicated in oil and gas operations with biocides, such as glutaraldehyde (Glut), tetrakis
(hydroxymethyl) phosphonium sulfate (THPS), and benzalkonium chloride (BAC), their response to these agents is not well known.
Whole genome microarrays of D. vulgaris treated with biocides well below the minimum inhibitory concentration showed that 256, 96, and 198 genes were responsive
to Glut, THPS, and BAC, respectively, and that these three commonly used biocides affect the physiology of the cell quite
differently. Glut induces expression of genes required to degrade or refold proteins inactivated by either chemical modification
or heat shock, whereas BAC appears to target ribosomal structure. THPS appears to primarily affect energy metabolism of SRB.
Mutants constructed for genes strongly up-regulated by Glut, were killed by Glut to a similar degree as the wild type. Hence,
it is difficult to achieve increased sensitivity to this biocide by single gene mutations, because Glut affects so many targets.
Our results increase understanding of the biocide's mode of action, allowing a more intelligent combination of mechanistically
different agents. This can reduce stress on budgets for chemicals and on the environment. 相似文献
57.
Therapeutic monoclonal antibodies have revolutionized the treatment of various inflammatory diseases. Immunogenicity against
these antibodies has been shown to be clinically important: it is associated with shorter response duration because of diminishing
concentrations in the blood and with infusion reactions. Concomitant immunomodulators in the form of methotrexate or azathioprine
reduced the immunogenicity of therapeutic antibodies in rheumatoid arthritis, Crohn disease, and juvenile idiopathic arthritis.
The occurrence of adverse events does not increase when immunomodulators are added to therapeutic antibodies. The mechanism
whereby methotrexate and azathioprine influence immunogenicity remains unclear. Evidence-based consensus on prescribing concomitant
immunomodulators is needed. 相似文献
58.
Sarina M. Hitzerd Sue Ellen Verbrugge Gert Ossenkoppele Gerrit Jansen Godefridus J. Peters 《Amino acids》2014,46(4):793-808
Aminopeptidases represent a class of (zinc) metalloenzymes that catalyze the cleavage of amino acids nearby the N-terminus of polypeptides, resulting in hydrolysis of peptide bonds. Aminopeptidases operate downstream of the ubiquitin–proteasome pathway and are implicated in the final step of intracellular protein degradation either by trimming proteasome-generated peptides for antigen presentation or full hydrolysis into free amino acids for recycling in renewed protein synthesis. This review focuses on the function and subcellular location of five key aminopeptidases (aminopeptidase N, leucine aminopeptidase, puromycin-sensitive aminopeptidase, leukotriene A4 hydrolase and endoplasmic reticulum aminopeptidase 1/2) and their association with different diseases, in particular cancer and their current position as target for therapeutic intervention by aminopeptidase inhibitors. Historically, bestatin was the first prototypical aminopeptidase inhibitor that entered the clinic 35 years ago and is still used for the treatment of lung cancer. More recently, new generation aminopeptidase inhibitors became available, including the aminopeptidase inhibitor prodrug tosedostat, which is currently tested in phase II clinical trials for acute myeloid leukemia. Beyond bestatin and tosedostat, medicinal chemistry has emerged with additional series of potential aminopeptidases inhibitors which are still in an early phase of (pre)clinical investigations. The expanded knowledge of the unique mechanism of action of aminopeptidases has revived interest in aminopeptidase inhibitors for drug combination regimens in anti-cancer treatment. In this context, this review will discuss relevant features and mechanisms of action of aminopeptidases and will also elaborate on factors contributing to aminopeptidase inhibitor efficacy and/or loss of efficacy due to drug resistance-related phenomena. Together, a growing body of data point to aminopeptidase inhibitors as attractive tools for combination chemotherapy, hence their implementation may be a step forward in a new era of personalized treatment of cancer patients. 相似文献
59.
60.
Hypovirus papain-like protease p29 suppresses RNA silencing in the natural fungal host and in a heterologous plant system 总被引:1,自引:0,他引:1
Virulence-attenuating hypoviruses of the species Cryphonectria hypovirus 1 (CHV1) encode a papain-like protease, p29, that shares similarities with the potyvirus-encoded suppressor of RNA silencing HC-Pro. We now report that hypovirus CHV1-EP713-encoded p29 can suppress RNA silencing in the natural host, the chestnut blight fungus Cryphonectria parasitica. Hairpin RNA-triggered silencing was suppressed in C. parasitica strains expressing p29, and transformation of a transgenic green fluorescent protein (GFP)-silenced strain with p29 resulted in an increased number of transformants with elevated GFP expression levels. The CHV1-EP713 p29 protein was also shown to suppress both virus-induced and agroinfiltration-induced RNA silencing and systemic spread of silencing in GFP-expressing transgenic Nicotiana benthamiana line 16c plants. The demonstration that a mycovirus encodes a suppressor of RNA silencing provides circumstantial evidence that RNA silencing in fungi may serve as an antiviral defense mechanism. The observation that a phylogenetically conserved protein of related plant and fungal viruses functions as a suppressor of RNA silencing in both fungi and plants indicates a level of conservation of the mechanisms underlying RNA silencing in these two groups of organisms. 相似文献