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991.
Enhanced anti-proliferative effects of combinatorial treatment of delta-tocopherol and resveratrol in human HMC-1 cells 总被引:1,自引:0,他引:1
The tocopherols (alpha, beta-, gamma-, and delta-tocopherol) and resveratrol are phytochemicals with alleged beneficial effects against atherosclerosis, vascular diseases and different cancers. They both can act as antioxidants, but they also modulate signal transduction and gene expression by non-antioxidant mechanisms. Here we wanted to determine whether the combined treatment of mast cells with the two compounds inhibits cell proliferation more efficiently when compared to individual treatments. Both compounds inhibit HMC-1 mastocytoma cell proliferation and reduce the activity of Protein Kinase B (PKB/Akt) by inhibiting its Ser473-phosphorylation. The combination of 50 microM delta-tocopherol and 50 microM resveratrol inhibits proliferation of HMC-1 cells more efficiently when compared to single treatments. In line with this, PKB Ser473-phosphorylation is inhibited best by delta-tocopherol and resveratrol combinatory treatment. Resveratrol acts more efficiently as an inhibitor of PKB phosphorylation than alpha-, beta-, gamma-tocopherols, whereas delta-tocopherol shows a stronger inhibition possibly as a result of its apoptotic secondary effects. Our data suggest that delta-tocopherol and resveratrol can act additively in reducing cell proliferation and PKB phosphorylation. The combination of phytochemicals with relatively broad specificity on enzymes involved in signal transduction and gene expression may increase their activity in disease prevention by modulating several different molecular targets. 相似文献
992.
Gerhard G Thallinger Kerstin Baumgartner Martin Pirklbauer Martina Uray Elke Pauritsch Gabor Mehes Charles R Buck Kurt Zatloukal Zlatko Trajanoski 《BMC bioinformatics》2007,8(1):81
Background
With the introduction of tissue microarrays (TMAs) researchers can investigate gene and protein expression in tissues on a high-throughput scale. TMAs generate a wealth of data calling for extended, high level data management. Enhanced data analysis and systematic data management are required for traceability and reproducibility of experiments and provision of results in a timely and reliable fashion. Robust and scalable applications have to be utilized, which allow secure data access, manipulation and evaluation for researchers from different laboratories. 相似文献993.
Houliston RS Koga M Li J Jarrell HC Richards JC Vitiazeva V Schweda EK Yuki N Gilbert M 《Biochemistry》2007,46(27):8164-8171
The non-typeable Haemophilus influenzae strain DH1 was isolated from a 25 year old male patient with Fisher syndrome, a postinfectious autoimmune condition characterized by the presence of anti-GQ1b IgG antibodies that target and initiate damage to peripheral nerves. DH1 was found to display an alphaNeuAc(2-8)alphaNeuAc(2-3)betaGal branch bound to the tetraheptosyl backbone core of its lipooligosaccharide (LOS). The novel sialylation pattern was found to be dependent on the activity of a bifunctional sialyltransferase, Lic3B, which catalyzes the addition of both the terminal and subterminal sialic acid residues. Patient serum IgGs bind to DH1 LOS, and the reactivity is significantly influenced by the presence of sialylated glycoforms. The display by DH1, of a surface glycan that mimics the terminal trisaccharide portion of disialosyl-containing gangliosides, provides strong evidence for its involvement in the development of Fisher syndrome. 相似文献
994.
Jürgen Lautermann H.‐G. Frank Klaus Jahnke Otto Traub Elke Winterhager 《Genesis (New York, N.Y. : 2000)》1999,25(4):306-311
Connexin proteins form transmembranous gap junction channels that connect adjacent cells. Connexin26 and connexin30 have been previously shown to be strongly expressed in the inner ear of adult rats and to be mainly colocalized. Because intercellular connections by gap junction proteins are crucial for maturation of different tissues, we investigated the developmental expression of connexin26 and connexin30 in pre‐ and postnatal rats using immunocytochemistry. In the rat otocyst, staining for connexin26 as well as for connexin30 appeared at the 17th day of gestation. However, at this stage, expression of connexin30 was low and restricted to the neurosensory epithelium. Beginning from the 3rd postnatal day connexin26 and ‐30 were expressed with highest immunoreaction in the spiral limbus, the neurosensory epithelium, and between the stria vascularis and the spiral ligament. Beginning from postnatal day 12 the staining pattern resembled that of adult animals, with additional strong staining between all fibrocytes of the spiral ligament. Double labeling experiments demonstrated strongest colocalization of both connexins between the stria vascularis and the spiral ligament. These results demonstrate that development of the cochlear gap junction system precedes the functional maturation of the rat inner ear, which takes place between the 2nd and 3rd postnatal week. In the cochlea of a 22‐week‐old human embryo, connexin26 and connexin30 could be detected in the lateral wall, suggesting that both connexins also play a crucial role in function of the human inner ear. Dev. Genet. 25:306–311, 1999. © 1999 Wiley‐Liss, Inc. 相似文献
995.
Tests are introduced which are designed to test for a nondecreasing ordered alternative among the survival functions of k populations consisting of multiple observations on each subject. Some of the observations could be right censored. A simulation study is conducted comparing the proposed tests on the basis of estimated power when the underlying distributions are multivariate normal. Equal sample sizes of 20 with 25% censoring, and 40 with both 25% and 50% censoring are considered for 3 and 4 populations. All of the tests hold their α‐values well. A recommendation is made as to the best overall test for the situations considered. 相似文献
996.
A procedure is presented to test for ordered alternatives in the k-sample case when the observations are subject to right censorship. This procedure is an extension of the one proposed by Hettmansperger and Norton (1987). The nondecreasing and umbrella alternatives are of particular interest. A Monte Carlo simulation study is done comparing this procedure with two other existing ones in the nondecreasing case. 相似文献
997.
Thomas Zimmermann Elke Kunisch Robert Pfeiffer Astrid Hirth Hans-Detlev Stahl Ulrich Sack Anke Laube Eckehard Liesaus Andreas Roth Ernesta Palombo-Kinne Frank Emmrich Raimund W Kinne 《Arthritis research & therapy》2000,3(1):72-20
To reduce culture artifacts by conventional repeated passaging and long-term culture in vitro, the isolation of synovial fibroblasts (SFB) was attempted from rheumatoid arthritis (RA) synovial membranes by trypsin/collagenase digest, short-term in vitro adherence (7 days), and negative isolation using magnetobead-coupled anti-CD14 monoclonal antibodies. This method yielded highly enriched SFB (85% prolyl-4-hydroxylase+/74% Thy-1/CD90+ cells; <2% contaminating macrophages; <1% leukocytes/endothelial cells) that, in comparison with conventional fourth-passage RA-SFB, showed a markedly different phenotype and significantly lower proliferation rates upon stimulation with platelet-derived growth factor and IL-1β. This isolation method is simple and reliable, and may yield cells with features closer to the in vivo configuration of RA-SFB by avoiding extended in vitro culture. 相似文献
998.
Filipe Marques Laurent Falquet Elke Vandewyer Isabel Beets Dominique A. Glauser 《PLoS genetics》2021,17(11)
In order to thrive in constantly changing environments, animals must adaptively respond to threatening events. Noxious stimuli are not only processed according to their absolute intensity, but also to their context. Adaptation processes can cause animals to habituate at different rates and degrees in response to permanent or repeated stimuli. Here, we used a forward genetic approach in Caenorhabditis elegans to identify a neuropeptidergic pathway, essential to prevent fast habituation and maintain robust withdrawal responses to repeated noxious stimuli. This pathway involves the FRPR-19A and FRPR-19B G-protein coupled receptor isoforms produced from the frpr-19 gene by alternative splicing. Loss or overexpression of each or both isoforms can impair withdrawal responses caused by the optogenetic activation of the polymodal FLP nociceptor neuron. Furthermore, we identified FLP-8 and FLP-14 as FRPR-19 ligands in vitro. flp-14, but not flp-8, was essential to promote withdrawal response and is part of the same genetic pathway as frpr-19 in vivo. Expression and cell-specific rescue analyses suggest that FRPR-19 acts both in the FLP nociceptive neurons and downstream interneurons, whereas FLP-14 acts from interneurons. Importantly, genetic impairment of the FLP-14/FRPR-19 pathway accelerated the habituation to repeated FLP-specific optogenetic activation, as well as to repeated noxious heat and harsh touch stimuli. Collectively, our data suggest that well-adjusted neuromodulation via the FLP-14/FRPR-19 pathway contributes to promote nociceptive signals in C. elegans and counteracts habituation processes that otherwise tend to rapidly reduce aversive responses to repeated noxious stimuli. 相似文献
999.
Shawn K. Milano Qingqiu Huang Thuy-Tien T. Nguyen Sekar Ramachandran Aaron Finke Irina Kriksunov David J. Schuller D. Marian Szebenyi Elke Arenholz Lee A. McDermott N. Sukumar Richard A. Cerione William P. Katt 《The Journal of biological chemistry》2022,298(2)
Cancer cells frequently exhibit uncoupling of the glycolytic pathway from the TCA cycle (i.e., the “Warburg effect”) and as a result, often become dependent on their ability to increase glutamine catabolism. The mitochondrial enzyme Glutaminase C (GAC) helps to satisfy this ‘glutamine addiction’ of cancer cells by catalyzing the hydrolysis of glutamine to glutamate, which is then converted to the TCA-cycle intermediate α-ketoglutarate. This makes GAC an intriguing drug target and spurred the molecules derived from bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (the so-called BPTES class of allosteric GAC inhibitors), including CB-839, which is currently in clinical trials. However, none of the drugs targeting GAC are yet approved for cancer treatment and their mechanism of action is not well understood. Here, we shed new light on the underlying basis for the differential potencies exhibited by members of the BPTES/CB-839 family of compounds, which could not previously be explained with standard cryo-cooled X-ray crystal structures of GAC bound to CB-839 or its analogs. Using an emerging technique known as serial room temperature crystallography, we were able to observe clear differences between the binding conformations of inhibitors with significantly different potencies. We also developed a computational model to further elucidate the molecular basis of differential inhibitor potency. We then corroborated the results from our modeling efforts using recently established fluorescence assays that directly read out inhibitor binding to GAC. Together, these findings should aid in future design of more potent GAC inhibitors with better clinical outlook. 相似文献
1000.
Rasoloharijaona Solofonirina Rakotosamimanana Berthe Zimmermann Elke 《International journal of primatology》2000,21(1):41-45
During a long-term field study on the behavioral ecology and communication of a population of the monogamous Milne-Edwards' sportive lemur (Lepilemur edwardsi) in NW-Madagascar, we recorded for the first time an infanticide in a nocturnal lemur. A male newcomer killed the infant of a female whose male partner had left her recently. Both the social-pathology and the sexual-selection hypotheses may explain infanticidal behavior in Lepilemur edwardsi. 相似文献