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991.
Development and organization of polarity-specific segregation of primary vestibular afferent fibers in mice 总被引:1,自引:0,他引:1
A striking feature of vestibular hair cells is the polarized arrangement of their stereocilia as the basis for their directional
sensitivity. In mammals, each of the vestibular end organs is characterized by a distinct distribution of these polarized
cells. We utilized the technique of post-fixation transganglionic neuronal tracing with fluorescent lipid soluble dyes in
embryonic and postnatal mice to investigate whether these polarity characteristics correlate with the pattern of connections
between the endorgans and their central targets; the vestibular nuclei and cerebellum. We found that the cerebellar and brainstem
projections develop independently from each other and have a non-overlapping distribution of neurons and afferents from E11.5
on. In addition, we show that the vestibular fibers projecting to the cerebellum originate preferentially from the lateral
half of the utricular macula and the medial half of the saccular macula. In contrast, the brainstem vestibular afferents originate
primarily from the medial half of the utricular macula and the lateral half of the saccular macula. This indicates that the
line of hair cell polarity reversal within the striola region segregates almost mutually exclusive central projections. A
possible interpretation of this feature is that this macular organization provides an inhibitory side-loop through the cerebellum
to produce synergistic tuning effects in the vestibular nuclei. The canal cristae project to the brainstem vestibular nuclei
and cerebellum, but the projection to the vestibulocerebellum originates preferentially from the superior half of each of
the cristae. The reason for this pattern is not clear, but it may compensate for unequal activation of crista hair cells or
may be an evolutionary atavism reflecting a different polarity organization in ancestral vertebrate ears. 相似文献
992.
Background
Nasopharyngeal carcinoma (NPC) is commonly found in Southern China and South East Asia. Epstein-Barr virus (EBV) infection is well associated with NPC and has been implicated in its pathogenesis. Moreover, various chromosome rearrangements were reported in NPC. However, the underlying mechanism of chromosome rearrangement remains unclear. Furthermore, the relationship between EBV and chromosome rearrangement with respect to the pathogenesis of NPC has not been established. We hypothesize that during virus- or stress-induced apoptosis, chromosomes are initially cleaved at the base of the chromatin loop domain structure. Upon DNA repair, cell may survive with rearranged chromosomes. 相似文献993.
The snubnose darters (Percidae: subgenus Ulocentra) are a group of small, brightly colored North American freshwater fish belonging to the genus Etheostoma. Phylogenetic relationships among snubnose species have been a challenge to resolve at all levels of divergence, from the monophyly of species to deeper relationships among subgenera. Here, we used amplified fragment length polymorphisms (AFLPs) to estimate phylogenetic relationships among species from three closely related subgenera: Ulocentra, Etheostoma, and Nanostoma. With nearly complete sampling of recognized species, our analysis yielded a robust tree with statistical support at all nodes. Support was strongest for shallower relationships; support for internal nodes was either comparable to or greater than that of previous studies based on mitochondrial sequence data. Most recovered relationships were consistent with earlier hypotheses based on morphology or mtDNA sequences, with the exception of Etheostoma histrio, which was recovered as sister to Ulocentra. Our analysis indicates that careful use of AFLPs can yield statistically robust estimates of evolutionary relationships across multiple levels of divergence. 相似文献
994.
Refined cancer models are required if researchers are to assess the burgeoning number of potential targets for cancer therapeutics in a clinically relevant context that allows a fast turnaround. Here we use tumor-associated genetic pathways to transform primary human epithelial cells from the epidermis, oropharynx, esophagus and cervix into genetically defined tumors in a human three-dimensional (3D) tissue environment that incorporates cell-populated stroma and intact basement membrane. These engineered organotypic tissues recapitulated natural features of tumor progression, including epithelial invasion through basement membrane, a complex process that is necessary for biological malignancy in 90% of human cancers. Invasion was rapid and was potentiated by stromal cells. Oncogenic signals in 3D tissue, but not 2D culture, resembled gene expression profiles from spontaneous human cancers. We screened 3D organotypic neoplasia with well-characterized signaling pathway inhibitors to distill a clinically faithful cancer gene signature. Multitissue 3D human tissue cancer models may provide an efficient and relevant complement to current approaches to characterizing cancer progression. 相似文献
995.
Phosphatidylinositol 3-kinase (PI3K) mediates receptor tyrosine kinase and G protein coupled receptor (GPCR) signaling by phosphorylating phosphoinositides to elicit various biological responses. Gαq has previously been shown to inhibit class IA PI3K by interacting with the p110α subunit. However, it is not known if PI3Ks can associate with other Gαq family members such as Gα16. Here, we demonstrated that class IA PI3Ks, p85/p110α and p85/p110β, could form stable complexes with wild type Gα16 and its constitutively active mutant (Gα16QL) in HEK293 cells. In contrast, no interaction between Gα16 and class IB PI3K was observed. The Gα16/p110α signaling complex could be detected in hematopoietic cells that endogenously express Gα16. Overexpression of class I PI3Ks did not inhibit Gα16QL-induced IP3 production and, unlike p63RhoGEF, class IA PI3Ks did not attenuate the binding of PLCβ2 to Gα16QL. On the contrary, the function of class IA PI3Ks was suppressed by Gα16QL as revealed by diminished production of PIP3 as well as inhibition of EGF-induced Akt phosphorylation. Taken together, these results suggest that Gα16 can bind to class IA PI3Ks and inhibit the PI3K signaling pathway. 相似文献
996.
Lachlan H. Yee Vibeke Aagaard Angela Johnstone Matthew Lee Staffan J. Kjelleberg Mike Manefield 《Biodegradation》2010,21(6):947-956
The biodegradation of chlorinated organics in vadose zone soils is challenging owing to the presence of oxygen, which inhibits
reductive dehalogenation reactions and consequently the growth of dehalorespiring microbes. In addition, the hydraulic conductivity
of vadose zone soils is typically high, hence attempts to remediate such zones with biostimulation solutions are often unsuccessful
due to the short residence times for these solutions to act upon the native bacterial community. In this study we have identified
sodium alginate as a hydrogel polymer that can be used to increase the residence time of a nutrient solution in an unsaturated
sandy soil. Additionally we have identified neutral red as a redox active compound that can catalyse the reductive dechlorination
of the chlorinated organic hexachloro-1,3-butadiene by activated sludge fed with lactate and acetate. Finally we have shown
that a nutrient solution amended with neutral red and sodium alginate can lower the redox potential and reduce hexachloro-1,3-butadiene
concentrations in a contaminated vadose zone soil. 相似文献
997.
Marko Milisavljevic Taryn Hearty Tony Y. T. Wong Elodie Portales-Casamar Elizabeth M. Simpson Wyeth W. Wasserman 《Mammalian genome》2010,21(5-6):224-230
Laboratory Animal Management Assistant (LAMA) is an internet-based system for tracking large laboratory mouse colonies. It has a user-friendly interface with powerful search capabilities that ease day-to-day tasks such as tracking breeding cages and weaning litters. LAMA was originally developed to manage hundreds of new mouse strains generated by a large functional genomics program, the Pleiades Promoter Project (http://www.pleiades.org). The software system has proven to be highly flexible, suitable for diverse management approaches to mouse colonies. It allows custom tagging and grouping of animals, simplifying project-specific handling and access to data. Finally, LAMA was developed in close collaboration with mouse technicians to ease the transition from paper- or Excel-based management systems to computerized tracking, allowing data export in a popular spreadsheet format and automatic printing of cage cards. LAMA is an open-access software tool, freely available to the research community at http://launchpad.net/mousedb. 相似文献
998.
Hung-Hsin Chao Cheng-Hsien Chen Ju-Chi Liu Jia-Wei Lin Kar-Lok Wong Tzu-Hurng Cheng 《The Journal of nutritional biochemistry》2010,21(7):580-588
The heart is unable to synthesize l-carnitine and is strictly dependent on the l-carnitine provided by the blood stream; however, additional studies are needed to better understand the mechanism of l-carnitine supplementation to the heart. The aim of this study was to evaluate the effects of l-carnitine on angiotensin II (Ang II)-induced cardiac fibroblast proliferation and to explore its intracellular mechanism(s). Cultured rat cardiac fibroblasts were pretreated with l-carnitine (1-30 mM) then stimulated with Ang II (100 nM). Ang II increased fibroblast proliferation and endothelin-1 expression, which were partially inhibited by l-carnitine. l-Carnitine also attenuated Ang II-induced NADPH oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, activator protein-1-mediated reporter activity and sphingosine-1-phosphate generation. In addition, l-carnitine increased prostacyclin (PGI2) generation in cardiac fibroblasts. siRNA transfection of PGI2 synthase significantly reduced l-carnitine-induced PGI2 and its anti-proliferation effects on cardiac fibroblasts. Furthermore, blockading potential PGI2 receptors, including immunoprecipitation (IP) receptors and peroxisome proliferator-activated receptors alpha (PPARα) and delta , revealed that siRNA-mediated blockage of PPARα considerably reduced the anti-proliferation effect of l-carnitine. In summary, these results suggest that l-carnitine attenuates Ang II-induced effects (including NADPH oxidase activation, sphingosine-1-phosphate generation and cell proliferation) in part through PGI2 and PPARα-signaling pathways. 相似文献
999.
1000.
Girijavallabhan VM Chen L Dai C Feltz RJ Firmansjah L Li D Kim SH Kozlowski JA Lavey BJ Kosinski A Piwinski JJ Popovici-Muller J Rizvi R Rosner KE Shankar BB Shih NY Siddiqui MA Tong L Wong MK Yang DY Yang L Yu W Zhou G Guo Z Orth P Madison V Bian H Lundell D Niu X Shah H Sun J Umland S 《Bioorganic & medicinal chemistry letters》2010,20(24):7283-7287
Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency (K(i)) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles. 相似文献