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991.
992.
Hung‐Yun Lin Dominique Delmas Ole Vang Tze‐Chen Hsieh Sharon Lin Guei‐Yun Cheng Hsiao‐Ling Chiang Chiao En Chen Heng‐Yuan Tang Dana R. Crawford Jacqueline Whang‐Peng Jaulang Hwang Leroy F. Liu Joseph M. Wu 《Journal of cellular biochemistry》2013,114(8):1940-1954
Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular‐signal‐regulated kinases (ERK)1/2‐ and p38 kinase‐dependent apoptosis in human ovarian cancer OVCAR‐3 cells, concomitant with an increase in the expression of COX‐2 and p53 phosphorylation. Blockade of cyclooxygenase‐2 (COX‐2) activity by siRNA or NS398 correspondingly inhibited ceramide‐induced p53 Ser‐15 phosphorylation and apoptosis; thus COX‐2 appears at the apex of the p38 kinase‐mediated signaling cascade induced by ceramide. Induction of apoptosis by ceramide or resveratrol was inhibited by the endocytosis inhibitor, cytochalasin D (CytD); however, cells exposed to resveratrol showed greater sensitivity than ceramide‐treated cells. Ceramide‐treated cells underwent a dose‐dependent reduction in trans‐membrane potential. Although both ceramide and resveratrol induced the expressions of caspase‐3 and ‐7, the effect of inducible COX‐2 was different in caspase‐7 expression induced by ceramide compared to resveratrol. In summary, resveratrol and ceramide converge on an endocytosis‐requiring, ERK1/2‐dependent signal transduction pathway and induction of COX‐expression as an essential molecular antecedent for subsequent p53‐dependent apoptosis. In addition, expressions of caspase‐3 and ‐7 are observed. However, a p38 kinase‐dependent signal transduction pathway and change in mitochondrial potential are also involved in ceramide‐induced apoptosis. J. Cell. Biochem. 114: 1940–1954, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
993.
Large numbers of protoplasts (106 to 3·2 × 107 per gram fresh weight) were routinely isolated from two Taiwanese species of Porphyra: P. dentata and P. crispata. Intermediate and final forms of regeneration were observed, including swollen cells, monospore-like cells, filaments, callus-like structures and bladelets. Regeneration of leafy plants was achieved from protoplasts of P. crispata, whereas only conchocelis-like filaments were regenerated from protoplasts of P. dentata. In this latter species, conchosporangia and monosporangia appeared on the filaments upon cultivation at 25 °C. The variability in regenerative patterns is discussed. 相似文献
994.
Chung-Jen Wang Chien-Chih Chen Huey-Jen Tsay Feng-Yi Chiang Mine-Fong Wu Young-Ji Shiao 《Journal of biomedical science》2013,20(1):55
Background
Microglial inflammation may significantly contribute to the pathology of Alzheimer’s disease. To examine the potential of Cudrania cochinchinensis to ameliorate amyloid β protein (Aβ)-induced microglia activation, BV-2 microglial cell line, and the ramified microglia in the primary glial mixed cultured were employed.Results
Lipopolysaccharide (LPS), Interferon-γ (IFN-γ), fibrillary Aβ (fAβ), or oligomeric Aβ (oAβ) were used to activate microglia. LPS and IFN-γ, but not Aβs, activated BV-2 cells to produce nitric oxide through an increase in inducible nitric oxide synthase (iNOS) expression without significant effects on cell viability of microglia. fAβ, but not oAβ, enhanced the IFN-γ-stimulated nitric oxide production and iNOS expression.The ethanol/water extracts of Cudrania cochinchinensis (CC-EW) and the purified isolated components (i.e. CCA to CCF) effectively reduced the nitric oxide production and iNOS expression stimulated by IFN-γ combined with fAβ. On the other hand, oAβ effectively activated the ramified microglia in mixed glial culture by observing the morphological alteration of the microglia from ramified to amoeboid. CC-EW and CCB effectively prohibit the Aβ-mediated morphological change of microglia. Furthermore, CC-EW and CCB effectively decreased Aβ deposition and remained Aβ in the conditioned medium suggesting the effect of CC-EW and CCB on promoting Aβ clearance. Results are expressed as mean ± S.D. and were analyzed by ANOVA with post-hoc multiple comparisons with a Bonferroni test.Conclusions
The components of Cudrania cochinchinensis including CC-EW and CCB are potential for novel therapeutic intervention for Alzheimer’s disease. 相似文献995.
Y.‐H. Lin Y.‐S. Chen H.‐C. Wu S.‐F. Pan B. Yu C.‐M. Chiang C.‐M. Chiu F. Yanagida 《Journal of applied microbiology》2013,114(2):299-307
996.
Talkowski ME Mullegama SV Rosenfeld JA van Bon BW Shen Y Repnikova EA Gastier-Foster J Thrush DL Kathiresan S Ruderfer DM Chiang C Hanscom C Ernst C Lindgren AM Morton CC An Y Astbury C Brueton LA Lichtenbelt KD Ades LC Fichera M Romano C Innis JW Williams CA Bartholomew D Van Allen MI Parikh A Zhang L Wu BL Pyatt RE Schwartz S Shaffer LG de Vries BB Gusella JF Elsea SH 《American journal of human genetics》2011,(4):551-563
Persons with neurodevelopmental disorders or autism spectrum disorder (ASD) often harbor chromosomal microdeletions, yet the individual genetic contributors within these regions have not been systematically evaluated. We established a consortium of clinical diagnostic and research laboratories to accumulate a large cohort with genetic alterations of chromosomal region 2q23.1 and acquired 65 subjects with microdeletion or translocation. We sequenced translocation breakpoints; aligned microdeletions to determine the critical region; assessed effects on mRNA expression; and examined medical records, photos, and clinical evaluations. We identified a single gene, methyl-CpG-binding domain 5 (MBD5), as the only locus that defined the critical region. Partial or complete deletion of MBD5 was associated with haploinsufficiency of mRNA expression, intellectual disability, epilepsy, and autistic features. Fourteen alterations, including partial deletions of noncoding regions not typically captured or considered pathogenic by current diagnostic screening, disrupted MBD5 alone. Expression profiles and clinical characteristics were largely indistinguishable between MBD5-specific alteration and deletion of the entire 2q23.1 interval. No copy-number alterations of MBD5 were observed in 7878 controls, suggesting MBD5 alterations are highly penetrant. We surveyed MBD5 coding variations among 747 ASD subjects compared to 2043 non-ASD subjects analyzed by whole-exome sequencing and detected an association with a highly conserved methyl-CpG-binding domain missense variant, p.79Gly>Glu (c.236G>A) (p = 0.012). These results suggest that genetic alterations of MBD5 cause features of 2q23.1 microdeletion syndrome and that this epigenetic regulator significantly contributes to ASD risk, warranting further consideration in research and clinical diagnostic screening and highlighting the importance of chromatin remodeling in the etiology of these complex disorders. 相似文献
997.
998.
Liu IF Chang SL Lo LW Hu YF Tuan TC Kong CW Wu TJ Chiang CE Chen SA Lin YJ 《International journal of biometeorology》2011,55(5):733-739
Some cardiovascular diseases are associated with seasonal or meteorological factors. We tried to identify the relationship
between meteorological parameters and the requirement for a permanent pacemaker (PPM) implantation for advanced sinus node
dysfunction (SND) and atrioventricular block (AVB). This study enrolled 656 patients (67% male, age = 76 ± 11 years) who underwent
a PPM implantation due to SND or AVB from January 2004 to December 2008. Using daily temperature, barometric pressure, humidity,
and daylight hour records from Taipei, we evaluated the effect of these meteorological parameters within different time periods
on the occurrence of SND and AVB. There were 355 patients in the SND group and 301 in the AVB group. In the AVB group, more
patients presented in the spring than in other seasons (P = 0.003). In the SND group, there was no relationship with the seasons (P = 0.137). The proportion of patients with AVB did not depend on the average temperature, barometric pressure, humidity, or
daylight hours within 3, 7, and 14 days prior to admission (P = NS). A temperature change of greater than 11°C within 30 days prior to admission was associated with a significantly higher
proportion of patients with advanced AVB compared to those with advanced SND (P = 0.009). Extreme change in temperature was the most independent predictor of the development of advanced AVB. The peak occurrence
of advanced AVB was in the spring. The occurrence of advanced AVB was associated with extreme temperature changes within 30 days,
especially in the spring. 相似文献
999.
Patel M Chiang TC Tran V Lee FJ Côté JF 《The Journal of biological chemistry》2011,286(45):38969-38979
The prototypical DOCK protein, DOCK180, is an evolutionarily conserved Rac regulator and is indispensable during processes such as cell migration and myoblast fusion. The biological activity of DOCK180 is tightly linked to its binding partner ELMO. We previously reported that autoinhibited ELMO proteins regulate signaling from this pathway. One mechanism to activate the ELMO-DOCK180 complex appears to be the recruitment of this complex to the membrane via the Ras-binding domain (RBD) of ELMO. In the present study, we aimed to identify novel ELMO-interacting proteins to further define the molecular events capable of controlling ELMO recruitment to the membrane. To do so, we performed two independent interaction screens: one specifically interrogated an active GTPase library while the other probed a brain cDNA library. Both methods converged on Arl4A, an Arf-related GTPase, as a specific ELMO interactor. Biochemically, Arl4A is constitutively GTP-loaded, and our binding assays confirm that both wild-type and constitutively active forms of the GTPase associate with ELMO. Mechanistically, we report that Arl4A binds the ELMO RBD and acts as a membrane localization signal for ELMO. In addition, we report that membrane targeting of ELMO via Arl4A promotes cytoskeletal reorganization including membrane ruffling and stress fiber disassembly via an ELMO-DOCK1800-Rac signaling pathway. We conclude that ELMO is capable of interacting with GTPases from Rho and Arf families, leading to the conclusion that ELMO contains a versatile RBD. Furthermore, via binding of an Arf family GTPase, the ELMO-DOCK180 is uniquely positioned at the membrane to activate Rac signaling and remodel the actin cytoskeleton. 相似文献
1000.
Chiang KC Yeh CN Chen HY Lee JM Juang HH Chen MF Takano M Kittaka A Chen TC 《Steroids》2011,76(13):1513-1519
The discovery that the active form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)2D] can modulate cellular proliferation and differentiation of cancer cells has led to its potential application as a chemotherapeutic agent to treat a variety of cancers. However, the use of 1α,25(OH)2D is limited due to its lethal side effect of hypercalcemia upon systemic administration. To overcome this drawback, numerous analogs have been synthesized. In this report, we examined the anti-proliferative activity of a new analog, 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3 (MART-10), in HepG2 liver cancer cells, and studied the potential mechanisms mediating this action. We found that MART-10 exhibited approximately 100-fold greater activity than 1α,25(OH)2D3 in inhibiting HepG2 cell proliferation as determined by cell number counting method. MART-10 was also approximately 100-fold more potent than 1α,25(OH)2D3 in the upregulation of p21 and p27, that in turn arrested HepG2 cells at the G0/G1 phase to a greater extent. Given that no active caspase 3 was detected and treatment with 1α,25(OH)2D3 or MART-10 did not further increase the fractions of apoptotic and necrosis cells over the controls, the growth-inhibitory effect of 1α,25(OH)2D3 and MART-10 on HepG2 cells may not involve apoptosis. Overall, our findings suggest that MART-10 is a good candidate as a novel therapeutic regimen against liver cancer. Further pre-clinical studies using animal models and the subsequent human clinical trials are warranted. 相似文献