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131.
132.
Yoshiyuki Wada Yuko Takami Masaki Tateishi Tomoki Ryu Kazuhiro Mikagi Hideki Saitsu 《PloS one》2016,11(1)
Background
Whether radiologically detected progressive disease (PD) is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC) is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC.Methods
We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3; 86 patients were ultimately enrolled.Results
Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group), whereas 39 did not (the discontinuous group). The median survival time (MST) in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01). The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01); it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03). In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01). Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval): ECOG PS <2 (0.290, 0.107–0.880), Barcelona Clinical Liver Cancer stage B (0.146, 0.047–0.457), serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355–5.691), and post-PD sorafenib administration (0.279, 0.150–0.510).Conclusion
Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients. 相似文献133.
134.
Takuya Hirose Naoki Takahashi Prasarn Tangkawattana Jun Minaguchi Shuji Mizumoto Shuhei Yamada Noriko Miyake Shujiro Hayashi Atsushi Hatamochi Jun Nakayama Tomomi Yamaguchi Ayana Hashimoto Yoshihiro Nomura Kazushige Takehana Tomoki Kosho Takafumi Watanabe 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(3):623-631
Musculocontractural Ehlers-Danlos syndrome (mcEDS) due to CHST14/D4ST1 deficiency (mcEDS-CHST14) is a recently delineated type of EDS caused by biallelic loss-of-function mutations in CHST14, which results in the depletion of dermatan sulfate (DS). Clinical characteristics of mcEDS-CHST14 consist of multiple malformations and progressive fragility-related manifestations, including skin hyperextensibility and fragility. Skin fragility is suspected to result from the impaired assembly of collagen fibrils caused by alteration of the glycosaminoglycan (GAG) chain of decorin-proteoglycan (PG) from DS to chondroitin sulfate (CS). This systematic investigation of the skin pathology of patients with mcEDS-CHST14 comprised both immunostaining of decorin and transmission electron microscopy-based cupromeronic blue staining to visualize GAG chains. Collagen fibrils were dispersed in the affected papillary to reticular dermis; in contrast, they were regularly and tightly assembled in controls. Moreover, the fibrils exhibited a perpendicular arrangement to the affected epidermis, whereas fibrils were parallel to control epidermis. Affected GAG chains were linear, stretching from the outer surface of collagen fibrils to adjacent fibrils; in contrast, those of controls were curved, maintaining close contact with attached collagen fibrils. This is the first observation of compositional alteration, from DS to CS, of GAG side chains, which caused structural alteration of GAG side chains and resulted in spatial disorganization of collagen networks; this presumably disrupted the ring-mesh structure of GAG side chains surrounding collagen fibrils. McEDS-CHST14 provides a critical example of the importance of DS in GAG side chains of decorin-PG during assembly of collagen fibrils in maintenance of connective tissues. 相似文献
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Horie Y Ito Y Ono M Moriwaki N Kato H Hamakubo Y Amano T Wachi M Shirai M Asayama M 《Molecular genetics and genomics : MGG》2007,278(3):331-346
Light-responsive gene expression is crucial to photosynthesizing organisms. Here, we studied functions of cis-elements (AU-box and SD sequences) and a trans-acting factor (ribonuclease, RNase) in light-responsive expression in cyanobacteria. The results indicated that AU-rich nucleotides
with an AU-box, UAAAUAAA, just upstream from an SD confer instability on the mRNA under darkness. An RNase E/G homologue,
Slr1129, of the cyanobacterium Synechocystis sp. strain PCC 6803 was purified and confirmed capable of endoribonucleolytic cleavage at the AU- (or AG)-rich sequences
in vitro. The cleavage depends on the primary target sequence and secondary structure of the mRNA. Complementation tests using
Escherichia coli rne/rng mutants showed that Slr1129 fulfilled the functions of both the RNase E and RNase G. An analysis of systematic mutations
in the AU-box and SD sequences showed that the cis-elements also affect significantly mRNA stability in light-responsive genes. These results strongly suggested that dark-induced
mRNA instability involves RNase E/G-type cleavage at the AU-box and SD sequences in cyanobacteria. The mechanical impact and
a possible common mechanism with RNases for light-responsive gene expression are discussed.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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139.
Yasuda T Hayakawa F Kurahashi S Sugimoto K Minami Y Tomita A Naoe T 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(12):6127-6134
140.
The activity patterns of the globus pallidus (GPe) and subthalamic nucleus (STN) are closely associated with motor function
and dysfunction in the basal ganglia. In the pathological state caused by dopamine depletion, the STN–GPe network exhibits
rhythmic synchronous activity accompanied by rebound bursts in the STN. Therefore, the mechanism of activity transition is
a key to understand basal ganglia functions. As synchronization in GPe neurons could induce pathological STN rebound bursts,
it is important to study how synchrony is generated in the GPe. To clarify this issue, we applied the phase-reduction technique
to a conductance-based GPe neuronal model in order to derive the phase response curve (PRC) and interaction function between
coupled GPe neurons. Using the PRC and interaction function, we studied how the steady-state activity of the GPe network depends
on intrinsic membrane properties, varying ionic conductances on the membrane. We noted that a change in persistent sodium
current, fast delayed rectifier Kv3 potassium current, M-type potassium current and small conductance calcium-dependent potassium
current influenced the PRC shape and the steady state. The effect of those currents on the PRC shape could be attributed to
extension of the firing period and reduction of the phase response immediately after an action potential. In particular, the
slow potassium current arising from the M-type potassium and the SK current was responsible for the reduction of the phase
response. These results suggest that the membrane property modulation controls synchronization/asynchronization in the GPe
and the pathological pattern of STN–GPe activity. 相似文献