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991.
Irina Ingold Michaela Aichler Elena Yefremova Antonella Roveri Katalin Buday Sebastian Doll Adrianne Tasdemir Nils Hoffard Wolfgang Wurst Axel Walch Fulvio Ursini José Pedro Friedmann Angeli Marcus Conrad 《The Journal of biological chemistry》2015,290(23):14668-14678
The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation. Recently, the cytosolic form of Gpx4 was identified as an upstream regulator of a novel form of non-apoptotic cell death, called ferroptosis, whereas the mitochondrial isoform of Gpx4 was previously shown to be crucial for male fertility. Here, we generated and analyzed mice with a targeted mutation of the active site selenocysteine of Gpx4 (Gpx4_U46S). Mice homozygous for Gpx4_U46S died at the same embryonic stage (E7.5) as Gpx4−/− embryos as expected. Surprisingly, male mice heterozygous for Gpx4_U46S presented subfertility. Subfertility was manifested in a reduced number of litters from heterozygous breeding and an impairment of spermatozoa to fertilize oocytes in vitro. Morphologically, sperm isolated from heterozygous Gpx4_U46S mice revealed many structural abnormalities particularly in the spermatozoa midpiece due to improper oxidation and polymerization of sperm capsular proteins and malformation of the mitochondrial capsule surrounding and stabilizing sperm mitochondria. These findings are reminiscent of sperm isolated from selenium-deprived rodents or from mice specifically lacking mitochondrial Gpx4. Due to a strongly facilitated incorporation of Ser in the polypeptide chain as compared with selenocysteine at the UGA codon, expression of the catalytically inactive Gpx4_U46S was found to be strongly increased. Because the stability of the mitochondrial capsule of mature spermatozoa depends on the moonlighting function of Gpx4 both as an enzyme oxidizing capsular protein thiols and as a structural protein, tightly controlled expression of functional Gpx4 emerges as a key for full male fertility. 相似文献
992.
Dual target strategy: combining distinct non‐dopaminergic treatments reduces neuronal cell loss and synergistically modulates l‐DOPA‐induced rotational behavior in a rodent model of Parkinson's disease 下载免费PDF全文
Marie‐Therese Fuzzati‐Armentero Silvia Cerri Giovanna Levandis Giulia Ambrosi Elena Montepeloso Gianfilippo Antoninetti Fabio Blandini Younis Baqi Christa E. Müller Rosaria Volpini Giulia Costa Nicola Simola Annalisa Pinna 《Journal of neurochemistry》2015,134(4):740-747
The glutamate metabotropic receptor 5 (mGluR5) and the adenosine A2A receptor (A2AR) represent major non‐dopaminergic therapeutic targets in Parkinson's disease (PD) to improve motor symptoms and slow down/revert disease progression. The 6‐hydroxydopamine rat model of PD was used to determine/compare the neuroprotective and behavioral impacts of single and combined administration of one mGluR5 antagonist, 2‐methyl‐6‐(phenylethynyl)pyridine (MPEP), and two A2AR antagonists, (E)‐phosphoric acid mono‐[3‐[8‐[2‐(3‐methoxyphenyl)vinyl]‐7‐methyl‐2,6‐dioxo‐1‐prop‐2‐ynyl‐1,2,6,7‐tetrahydropurin‐3‐yl]propyl] (MSX‐3) and 8‐ethoxy‐9‐ethyladenine (ANR 94). Chronic treatment with MPEP or MSX‐3 alone, but not with ANR 94, reduced the toxin‐induced loss of dopaminergic neurons in the substantia nigra pars compacta. Combining MSX‐3 and MPEP further improved the neuroprotective effect of either antagonists. At the behavioral level, ANR 94 and MSX‐3 given alone significantly potentiated l ‐DOPA‐induced turning behavior. Combination of either A2AR antagonists with MPEP synergistically increased L‐DOPA‐induced turning. This effect was dose‐dependent and required subthreshold drug concentration, which per se had no motor stimulating effect. Our findings suggest that co‐treatment with A2AR and mGluR5 antagonists provides better therapeutic benefits than those produced by either drug alone. Our study sheds some light on the efficacy and advantages of combined non‐dopaminergic PD treatment using low drug concentration and establishes the basis for in‐depth studies to identify optimal doses at which these drugs reach highest efficacy.
993.
Christine A. Bricault James M. Kovacs Joseph P. Nkolola Karina Yusim Elena E. Giorgi Jennifer L. Shields James Perry Christy L. Lavine Ann Cheung Katharine Ellingson-Strouss Cecelia Rademeyer Glenda E. Gray Carolyn Williamson Leonidas Stamatatos Michael S. Seaman Bette T. Korber Bing Chen Dan H. Barouch 《Journal of virology》2015,89(5):2507-2519
994.
Michael Lauck Sergey V. Alkhovsky Yīmíng Bào Adam L. Bailey Zinaida V. Shevtsova Alexey M. Shchetinin Tatyana V. Vishnevskaya Matthew G. Lackemeyer Elena Postnikova Steven Mazur Jiro Wada Sheli R. Radoshitzky Thomas C. Friedrich Boris A. Lapin Petr G. Deriabin Peter B. Jahrling Tony L. Goldberg David H. O'Connor Jens H. Kuhn 《Journal of virology》2015,89(15):8082-8087
Simian hemorrhagic fever (SHF) is lethal for macaques. Based on clinical presentation and serological diagnosis, all reported SHF outbreaks were thought to be caused by different strains of the same virus, simian hemorrhagic fever virus (SHFV; Arteriviridae). Here we show that the SHF outbreaks in Sukhumi in 1964 and in Alamogordo in 1989 were caused not by SHFV but by two novel divergent arteriviruses. Our results indicate that multiple divergent simian arteriviruses can cause SHF. 相似文献
995.
996.
997.
998.
The interplay between event and background sedimentation and the origin of fossil‐rich carbonate concretions: a case study in Permian rocks of the Paraná Basin,Brazil 下载免费PDF全文
João G. Bondioli Suzana A. Matos Lucas V. Warren Mário L. Assine Cláudio Riccomini Marcello G. Simões 《Lethaia: An International Journal of Palaeontology and Stratigraphy》2015,48(4):522-539
The Permian Serra Alta Formation was generated under transgressive conditions within a large, calm epeiric sea. A monotonous succession of ‘barren’, massive mudstones deposited under oxygen‐deficient conditions (mainly below storm wave base) is the main lithofacies of this unit. Fossils are generally rare and diluted in the matrix, but certain intervals contain shell‐rich concentrations with well‐preserved, closed articulated bivalves, mixed with shells and comminuted debris with variable quality of preservation, all encased in carbonate concretions. Two main scenarios may account for the origin of these bivalve‐rich concretions (i.e. unique events in sea‐water chemistry or unique burial‐starvation couplets). Sedimentological and taphonomic information indicates that the final deposition of the original shell‐rich mudstone intervals was probably tied to episodic influx of fine‐grained sediments in distal settings. Moderate bioturbation is also recorded suggesting low rates of sedimentation prior to early diagenesis. Hence, the fossil concentrations in concretions were formed due to the interplay of event and background sedimentation. These are internally simple concentrations with complex depositional histories. The concretion‐bearing beds are not randomly distributed in the Serra Alta Formation. Rather, they are found in the sparsely fossiliferous offshore deposits of the basal to intermediate portions of the unit. Thus, the concretionary mudstone beds and associated deposits are preserved in particular intervals and can be tracked for kilometres. This indicates that the conditions essential for concretion development existed only at particular stratigraphical intervals. Finally, our study strongly corroborates the idea that concretions are critical sources of sedimentological, taphonomic and stratigraphical information. 相似文献
999.
1000.
Elena Ciani Emiliano Lasagna Mariasilvia D’Andrea Ingrid Alloggio Fabio Marroni Simone Ceccobelli Juan V. Delgado Bermejo Francesca M. Sarti James Kijas Johannes A. Lenstra Fabio Pilla the International Sheep Genomics Consortium 《遗传、选种与进化》2015,47(1)