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91.
Diana Marcela Penarete-Vargas Ana?s Boisson Serge Urbach Hervé Chantelauze Suzanne Peyrottes Laurent Fraisse Henri J. Vial 《PloS one》2014,9(12)
Plasmodium falciparum is responsible for severe malaria which is one of the most prevalent and deadly infectious diseases in the world. The antimalarial therapeutic arsenal is hampered by the onset of resistance to all known pharmacological classes of compounds, so new drugs with novel mechanisms of action are critically needed. Albitiazolium is a clinical antimalarial candidate from a series of choline analogs designed to inhibit plasmodial phospholipid metabolism. Here we developed an original chemical proteomic approach to identify parasite proteins targeted by albitiazolium during their native interaction in living parasites. We designed a bifunctional albitiazolium-derived compound (photoactivable and clickable) to covalently crosslink drug–interacting parasite proteins in situ followed by their isolation via click chemistry reactions. Mass spectrometry analysis of drug–interacting proteins and subsequent clustering on gene ontology terms revealed parasite proteins involved in lipid metabolic activities and, interestingly, also in lipid binding, transport, and vesicular transport functions. In accordance with this, the albitiazolium-derivative was localized in the endoplasmic reticulum and trans-Golgi network of P. falciparum. Importantly, during competitive assays with albitiazolium, the binding of choline/ethanolamine phosphotransferase (the enzyme involved in the last step of phosphatidylcholine synthesis) was substantially displaced, thus confirming the efficiency of this strategy for searching albitiazolium targets. 相似文献
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There have been several reports that individuals with Fragile X syndrome (FXS) and animal models of FXS have communication deficits. The present study utilized two different call classification taxonomies to examine the sex‐specificity of ultrasonic vocalization (USV) production on postnatal day (PD8) in the FVB strain of Fmr1 knockout (KO) mice. One classification protocol requires the investigator to score each call by hand, while the other protocol uses an automated algorithm. Results using the hand‐scoring protocol indicated that male Fmr1 KO mice exhibited longer calls (P = .03) than wild types on PD8. Male KOs also produced fewer complex, composite, downward, short and two‐syllable call‐types, as well as more frequency steps and chevron call‐types. Female heterozygotes exhibited no significant changes in acoustic or temporal aspects of calls, yet showed significant changes in call‐type production proportions across two different classification taxonomies (P < .001). They exhibited increased production of harmonic and frequency steps calls, as well as fewer chevron, downward and short calls. According to the second high‐throughput analysis, female heterozygotes produced significantly fewer single‐type and more multiple‐type syllables, unlike male KOs that showed no changes in these aspects of syllable production. Finally, we correlated both scoring methods and found a high level of correlation between the two methods. These results contribute further knowledge of sex differences in USV calling behavior for Fmr1 heterozygote and KO mice and provide a foundation for the use of high‐throughput analysis of neonatal USVs. 相似文献
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Seymour Colleen L. Milton Suzanne J. Altwegg Res Joseph Grant S. Dean W. Richard J. 《Ecosystems》2020,23(1):175-187
Ecosystems - Addition of nitrogen (N) to rangeland that has been degraded through overgrazing or drought can hasten vegetation recovery. Additional N may influence temporal stability of vegetation... 相似文献
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Suzanne M. Marselis Katharine Abernethy Alfonso Alonso John Armston Timothy R. Baker Jean‐Francois Bastin Jan Bogaert Doreen S. Boyd Pascal Boeckx David F. R. P. Burslem Robin Chazdon David B. Clark David Coomes Laura Duncanson Steven Hancock Ross Hill Chris Hopkinson Elizabeth Kearsley James R. Kellner David Kenfack Nicolas Labrire Simon L. Lewis David Minor Herv Memiaghe Abel Monteagudo Reuben Nilus Michael O'Brien Oliver L. Phillips John Poulsen Hao Tang Hans Verbeeck Ralph Dubayah 《Global Ecology and Biogeography》2020,29(10):1799-1816
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Lela Jackson Androniqi Qifti Katherine M. Pearce Suzanne Scarlata 《Protein science : a publication of the Protein Society》2020,29(6):1258-1268
Some proteins can serve multiple functions depending on different cellular conditions. An example of a bifunctional protein is inositide‐specific mammalian phospholipase Cβ (PLCβ). PLCβ is activated by G proteins in response to hormones and neurotransmitters to increase intracellular calcium. Recently, alternate cellular function(s) of PLCβ have become uncovered. However, the conditions that allow these different functions to be operative are unclear. Like many mammalian proteins, PLCβ has a conserved catalytic core along with several regulatory domains. These domains modulate the intensity and duration of calcium signals in response to external sensory information, and allow this enzyme to inhibit protein translation in a noncatalytic manner. In this review, we first describe PLCβ's cellular functions and regulation of the switching between these functions, and then discuss the thermodynamic considerations that offer insight into how cells manage multiple and competitive associations allowing them to rapidly shift between functional states. 相似文献