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991.
Peter D. Simpson Betty A. Eipper Maximiliano J. Katz Lautaro Gandara Pablo Wappner Roman Fischer Emma J. Hodson Peter J. Ratcliffe Norma Masson 《The Journal of biological chemistry》2015,290(41):24891-24901
Interactions between biological pathways and molecular oxygen require robust mechanisms for detecting and responding to changes in cellular oxygen availability, to support oxygen homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) catalyzes a two-step reaction resulting in the C-terminal amidation of peptides, a process important for their stability and biological activity. Here we show that in human, mouse, and insect cells, peptide amidation is exquisitely sensitive to hypoxia. Different amidation events on chromogranin A, and on peptides processed from proopiomelanocortin, manifest similar striking sensitivity to hypoxia in a range of neuroendocrine cells, being progressively inhibited from mild (7% O2) to severe (1% O2) hypoxia. In developing Drosophila melanogaster larvae, FMRF amidation in thoracic ventral (Tv) neurons is strikingly suppressed by hypoxia. Our findings have thus defined a novel monooxygenase-based oxygen sensing mechanism that has the capacity to signal changes in oxygen availability to peptidergic pathways. 相似文献
992.
Roman Przymusiński Renata Rucińska-Sobkowiak Bogna Ilska Edward A. Gwóźdź 《Acta Physiologiae Plantarum》2007,29(5):411-416
In an earlier work using tissue printing method, we found that the PR-10 stress protein was observed in leaf petiole of lupin
seedling where lead was not detected (Przymusiński et al. 2001). These results suggested the presence of substance(s) mediating a signal transduction from directly affected cells to distant
organs. As the hydrogen peroxide was found to be involved in signal transduction pathway, in the present paper, we analysed
the level of H2O2 in the organ of lupin seedlings exposed to Pb2+ with spectrophotometric method and tissue printing technique. It was unequivocally demonstrated that the level of H2O2 and the activity of peroxidase increased in every tested organ of lead-treated lupin seedling. Both the level of H2O2 and the activity of POX were correlated with amount of Pb2+ ions in the cells (Przymusiński et al. 2001) and decreased in tissues more and more distant from the site of metal application. On the other hand, there was no correlation
between the histological localization of H2O2 and peroxidase. Our results seem to confirm the hypothesis that H2O2 may act as a signalling substance involved in the induction of PR protein synthesis. It was indicated that there is high
degree of correlation between the localization of H2O2 and the histological localization of PR-10 proteins (Przymusiński et al. 2001) in every tested organ of lupin seedling. The presented hypothesis is also supported by the fact that H2O2 and PR-10 proteins are detected in organs and tissues where Pb2+ was not found at all. 相似文献
993.
Mingfeng Yu Sandra Ast Qun Yu Anthony T. S. Lo Roman Flehr Matthew H. Todd Peter J. Rutledge 《PloS one》2014,9(7)
Ligands incorporating a tetraazamacrocycle receptor, a ‘click’- derived triazole and a 1,8-naphthalimide fluorophore have proven utility as probes for metal ions. Three new cyclam-based molecular probes are reported, in which a piperidinyl group has been introduced at the 4-position of the naphthalimide fluorophore. These compounds have been synthesized using the copper(I)-catalyzed azide-alkyne Huisgen cycloaddition and their photophysical properties studied in detail. The alkylamino group induces the expected red-shift in absorption and emission spectra relative to the simple naphthalimide derivatives and gives rise to extended fluorescence lifetimes in aqueous buffer. The photophysical properties of these systems are shown to be highly solvent-dependent. Screening the fluorescence responses of the new conjugates to a wide variety of metal ions reveals significant and selective fluorescence quenching in the presence of copper(II), yet no fluorescence enhancement with zinc(II) as observed previously for the simple naphthalimide derivatives. Reasons for this different behaviour are proposed. Cytotoxicity testing shows that these new cyclam-triazole-dye conjugates display little or no toxicity against either DLD-1 colon carcinoma cells or MDA-MB-231 breast carcinoma cells, suggesting a potential role for these and related systems in biological sensing applications. 相似文献
994.
995.
Catarina Magalh?es Mark I. Stevens S. Craig Cary Becky A. Ball Bryan C. Storey Diana H. Wall Roman Türk Ulrike Ruprecht 《PloS one》2012,7(9)
Multitrophic communities that maintain the functionality of the extreme Antarctic terrestrial ecosystems, while the simplest of any natural community, are still challenging our knowledge about the limits to life on earth. In this study, we describe and interpret the linkage between the diversity of different trophic level communities to the geological morphology and soil geochemistry in the remote Transantarctic Mountains (Darwin Mountains, 80°S). We examined the distribution and diversity of biota (bacteria, cyanobacteria, lichens, algae, invertebrates) with respect to elevation, age of glacial drift sheets, and soil physicochemistry. Results showed an abiotic spatial gradient with respect to the diversity of the organisms across different trophic levels. More complex communities, in terms of trophic level diversity, were related to the weakly developed younger drifts (Hatherton and Britannia) with higher soil C/N ratio and lower total soluble salts content (thus lower conductivity). Our results indicate that an increase of ion concentration from younger to older drift regions drives a succession of complex to more simple communities, in terms of number of trophic levels and diversity within each group of organisms analysed. This study revealed that integrating diversity across multi-trophic levels of biotic communities with abiotic spatial heterogeneity and geological history is fundamental to understand environmental constraints influencing biological distribution in Antarctic soil ecosystems. 相似文献
996.
997.
Hyock Joo Kwon Weimei Xing Katie Chan Anita Niedziela-Majka Katherine M. Brendza Thorsten Kirschberg Darryl Kato John O. Link Guofeng Cheng Xiaohong Liu Roman Sakowicz 《PloS one》2015,10(4)
Ledipasvir, a direct acting antiviral agent (DAA) targeting the Hepatitis C Virus NS5A protein, exhibits picomolar activity in replicon cells. While its mechanism of action is unclear, mutations that confer resistance to ledipasvir in HCV replicon cells are located in NS5A, suggesting that NS5A is the direct target of ledipasvir. To date co-precipitation and cross-linking experiments in replicon or NS5A transfected cells have not conclusively shown a direct, specific interaction between NS5A and ledipasvir. Using recombinant, full length NS5A, we show that ledipasvir binds directly, with high affinity and specificity, to NS5A. Ledipasvir binding to recombinant NS5A is saturable with a dissociation constant in the low nanomolar range. A mutant form of NS5A (Y93H) that confers resistance to ledipasvir shows diminished binding to ledipasvir. The current study shows that ledipasvir inhibits NS5A through direct binding and that resistance to ledipasvir is the result of a reduction in binding affinity to NS5A mutants. 相似文献
998.
Hélène Bonsang-Kitzis Léonor Chaltier Lisa Belin Alexia Savignoni Roman Rouzier Marie-Paule Sablin Florence Lerebours Fran?ois-Clément Bidard Paul Cottu Xavier Sastre-Garau Marick Laé Jean-Yves Pierga Fabien Reyal 《PloS one》2015,10(12)
BackgroundTriple-negative breast cancers (TNBC) are a specific subtype of breast cancers with a particularly poor prognosis. However, it is a very heterogeneous subgroup in terms of clinical behavior and sensitivity to systemic treatments. Thus, the identification of risk factors specifically associated with those tumors still represents a major challenge. A therapeutic strategy increasingly used for TNBC patients is neoadjuvant chemotherapy (NAC). Only a subset of patients achieves a pathologic complete response (pCR) after NAC and have a better outcome than patients with residual disease.PurposeThe aim of this study is to identify clinical factors associated with the metastatic-free survival in TNBC patients who received NAC.MethodsWe analyzed 326 cT1-3N1-3M0 patients with ductal infiltrating TNBC treated by NAC. The survival analysis was performed using a Cox proportional hazard model to determine clinical features associated with prognosis on the whole TNBC dataset. In addition, we built a recursive partitioning tree in order to identify additional clinical features associated with prognosis in specific subgroups of TNBC patients.ResultsWe identified the lymph node involvement after NAC as the only clinical feature significantly associated with a poor prognosis using a Cox multivariate model (HR = 3.89 [2.42–6.25], p<0.0001). Using our recursive partitioning tree, we were able to distinguish 5 subgroups of TNBC patients with different prognosis. For patients without lymph node involvement after NAC, obesity was significantly associated with a poor prognosis (HR = 2.64 [1.28–5.55]). As for patients with lymph node involvement after NAC, the pre-menopausal status in grade III tumors was associated with poor prognosis (HR = 9.68 [5.71–18.31]).ConclusionThis study demonstrates that axillary lymph node status after NAC is the major prognostic factor for triple-negative breast cancers. Moreover, we identified body mass index and menopausal status as two other promising prognostic factors in this breast cancer subgroup. Using these clinical factors, we were able to classify TNBC patients in 5 subgroups, for which pre-menopausal patients with grade III tumors and lymph node involvement after NAC have the worse prognosis. 相似文献
999.
Miroslaw Janczura Grazyna Bochenek Roman Nowobilski Jerzy Dropinski Katarzyna Kotula-Horowitz Bartosz Laskowicz Andrzej Stanisz Jacek Lelakowski Teresa Domagala 《PloS one》2015,10(8)