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91.
92.
The potential of quantitative proteomic analysis to predict carcinogenicity of chemical compounds was investigated. Using 2D-DIGE, we analyzed the effects of 63 chemical compounds on protein expression in the rat liver after 28 daily doses. Types of carcinogens were categorized depending on the species and organ specificity. The carcinogen characteristic proteins for each classification were identified by Welch's t value. For evaluation of the predictive concordance we used support vector machines. The rat hepatic carcinogen-specific classification gave higher concordance than the other classification. The generalization performance was measured by leave-one-out cross-validation. For genotoxic and non-genotoxic compounds, a concordance of 79.3 and 76.5%, respectively, was obtained by the top 30 ranked proteins with Welch's t value. Furthermore, we found that the increase of the expression level of the stress response proteins as the common feature of poorly predicted chemical compounds in the leave-20%-out cross-validation. Quantitative proteomics could be promising technique for developing biomarker panels that can be used for carcinogenicity prediction. The list of proteins identified in this study and the zoomed gel images of the top ranked proteins in statistic analysis are provided in Supplementary Data. 相似文献
93.
Uchii Kimiko Wakimura Kei Kikko Takeshi Yonekura Ryuji Kawaguchi Riho Komada Honoka Yamanaka Hiroki Kenzaka Takehiko Tani Katsuji 《Limnology》2022,23(1):49-56
Limnology - Gnathopogon caerulescens is an endangered but commercially important fish in Lake Biwa, Japan. The population size of G. caerulescens has drastically reduced in the past decades, and... 相似文献
94.
Goki Tanaka Tomoyuki Yamanaka Yoshiaki Furukawa Naoko Kajimura Kaoru Mitsuoka Nobuyuki Nukina 《生物化学与生物物理学报:疾病的分子基础》2019,1865(6):1410-1420
Synucleinopathies comprise a diverse group of neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies, and multiple system atrophy. These share a common pathological feature, the deposition of alpha-synuclein (a-syn) in neurons or oligodendroglia. A-syn is highly conserved in vertebrates, but the primary sequence of mouse a-syn differs from that of human at seven positions. However, structural differences of their aggregates remain to be fully characterized. In this study, we found that human and mouse a-syn aggregated in vitro formed morphologically distinct amyloid fibrils exhibiting twisted and straight structures, respectively. Furthermore, we identified different protease-resistant core regions, long and short, in human and mouse a-syn aggregates. Interestingly, among the seven unconserved amino acids, only A53T substitution, one of the familial PD mutations, was responsible for structural conversion to the straight-type. Finally, we checked whether the structural differences are transmissible by seeding and found that human a-syn seeded with A53T aggregates formed straight-type fibrils with short protease-resistant cores. These results suggest that a-syn aggregates form sequence-dependent polymorphic fibrils upon spontaneous aggregation but become seed structure-dependent upon seeding. 相似文献
95.
EGF family ligand-dependent phenotypic modulation of smooth muscle cells through EGF receptor 总被引:3,自引:0,他引:3
Yamanaka Y Hayashi K Komurasaki T Morimoto S Ogihara T Sobue K 《Biochemical and biophysical research communications》2001,281(2):373-377
The phenotypic modulation of smooth muscle cells (SMCs) is closely associated with the development and progression of various SMC diseases. We investigated the molecular mechanism of phenotypic modulation triggered by EGF family ligands using a primary culture system of differentiated SMCs. Among four EGF-receptor (EGFR) family members, the EGFR was solely activated by EGF, heparin-binding EGF (HB-EGF), transforming growth factor alpha (TGF alpha), epiregulin (ER), and betacellulin (BTC), resulting in induction of phenotypic modulation of SMCs. This effect was mediated through the coordinated activation of the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) pathways. These results suggest that EGF family ligand- and EGFR-triggered signaling pathways are critically involved in the phenotypic modulation of SMCs. 相似文献
96.
The ATP hydrolysis mechanism of myosin was studied using quantum chemical (QM) and molecular dynamics calculations. The initial model compound for QM calculations was constructed on the basis of the energy-minimized structure of the myosin(S1dc)-ATP complex, which was determined by molecular mechanics calculations. The result of QM calculations suggested that the ATP hydrolysis mechanism of myosin consists of a single elementary reaction in which a water molecule nucleophilically attacked gamma-phosphorus of ATP. In addition, we performed molecular dynamics simulations of the initial and final states of the ATP hydrolysis reaction, that is, the myosin-ATP and myosin-ADP.Pi complexes. These calculations revealed roles of several amino acid residues (Lys185, Thr186, Ser237, Arg238, and Glu459) in the ATPase pocket. Lys185 maintains the conformation of beta- and gamma-phosphate groups of ATP by forming the hydrogen bonds. Thr186 and Ser237 are coordinated to a Mg(2+) ion, which interacts with the phosphates of ATP and therefore contributes to the stabilization of the ATP structure. Arg238 and Glu459, which consisted of the gate of the ATPase pocket, retain the water molecule acting on the hydrolysis at the appropriate position for initiating the hydrolysis. 相似文献
97.
Nonsense and frameshift mutations in ZFHX1B, encoding Smad-interacting protein 1, cause a complex developmental disorder with a great variety of clinical features 下载免费PDF全文
Yamada K Yamada Y Nomura N Miura K Wakako R Hayakawa C Matsumoto A Kumagai T Yoshimura I Miyazaki S Kato K Sonta S Ono H Yamanaka T Nagaya M Wakamatsu N 《American journal of human genetics》2001,69(6):1178-1185
Mutations in ZFHX1B, encoding Smad-interacting protein 1 (SIP1), have been recently reported to cause a form of Hirschsprung disease (HSCR). Patients with ZFHX1B deficiency typically show mental retardation, delayed motor development, epilepsy, microcephaly, distinct facial features, and/or congenital heart disease, in addition to the cardinal form of HSCR. To investigate the breadth of clinical variation, we studied DNA samples from six patients with clinical profiles quite similar to those described elsewhere for ZFHX1B deficiency, except that they did not have HSCR. The results showed the previously reported R695X mutation to be present in three cases, with three novel mutations-a 2-bp insertion (760insCA resulting in 254fs262X), a single-base deletion (270delG resulting in 91fs107X), and a 2-bp deletion (2178delTT resulting in 727fs754X)-newly identified in the other three. All mutations occurred in one allele and were de novo events. These results demonstrate that ZFHX1B deficiency is an autosomal dominant complex developmental disorder and that individuals with functional null mutations present with mental retardation, delayed motor development, epilepsy, and a wide spectrum of clinically heterogeneous features suggestive of neurocristopathies at the cephalic, cardiac, and vagal levels. 相似文献
98.
Sato M Tsuji NM Gotoh H Yamashita K Hashimoto K Tadotsu N Yamanaka H Sekikawa K Hashimoto Y 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(8):4701-4709
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia with small platelets, severe eczema, and recurrent infections due to defects in the immune system. The disease arises from mutations in the gene encoding the WAS protein (WASP), which plays a role as an adaptor molecule in signal transduction accompanied by cytoskeletal rearrangement in T cells. To investigate the functional domain of WASP, we developed transgenic mice overexpressing the WASP N-terminal region (exon 1-5) including the Ena/VASP homology 1 (pleckstrin homology/WASP homology 1) domain, in which the majority of mutations in WAS patients have been observed. WASP transgenic mice develop and grow normally under the specific pathogen-free environment, and showed normal lymphocyte development. However, proliferative responses and cytokine production induced by TCR stimulation were strongly inhibited in transgenic mice, whereas Ag receptor capping and actin polymerization were normal. These findings suggest that overexpressed Ena/VASP homology 1 (pleckstrin homology/WASP homology 1) domain of WASP inhibits the signaling from TCR without coupling of cytoskeletal rearrangement. WASP transgenic mice shown here could be valuable tools for further understanding the WASP-mediated processes. 相似文献
99.
Protective effect of imidaprilat, an angiotensin-converting enzyme inhibitor on *OH generation in rat myocardium 总被引:5,自引:0,他引:5
We used a flexibly mounted microdialysis technique to the hearts of rats and examined the protective effect of imidaprilat, an angiotensin-converting enzyme (ACE) inhibitor, on the production of hydroxyl free radical (*OH) generation. A microdialysis probe was implanted into the left ventricular myocardium, and dialysate norepinephrine (NE) concentrations were measured as an index of myocardial interstitial NE levels. Sodium salicylate in Ringer's solution (0.5 nmol/microl/min) was directly infused through a microdialysis probe to detect the generation of *OH reflected by the formation of dihydroxybenzoic acid (DHBA) in rat myocardium. When tyramine (1 mM) was directly infused through the microdialysis probe, the level of NE significantly increased in the dialysate and the level of NE increased by 128 +/- 43%. Imidaprilat (5, 25 and 50 microM) decreased the level of tyramine (1 mM)-induced NE in a concentration-dependent manner. Tyramine clearly produced an increase in *OH formation. In the presence of imidaprilat (50 microM), tyramine failed to increase both 2,3- and 2,5-dihydroxylation. Therefore, the effects of imidaprilat on the *OH generation in the sympathetic nerve blockaded hearts by reserpine treatment were not observed. Moreover, to examine the effect of imidaprilat on *OH formation by ischemia/reperfusion of the myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery. When the heart was reperfused, elevation of NE and 2,3- and 2,5-DHBA in imidaprilat (50 microM)-pretreated animals was not observed in the heart dialysate. Imidaprilat 2.5 mg/kg i.p. pretreatment at 5 h before coronary occlusion significantly blunted the rise of serum creatine phosphokinase and improved the electrocardiogram 2 h after coronary occlusion. These results suggest that imidaprilat, an ACE inhibitor, is associated with cardioprotective effect due to the suppression of NE-induced *OH generation. 相似文献
100.
CspI, the ninth member of the CspA family of Escherichia coli, is induced upon cold shock 总被引:2,自引:0,他引:2 下载免费PDF全文
Escherichia coli contains the CspA family, consisting of nine proteins (CspA to CspI), in which CspA, CspB, and CspG have been shown to be cold shock inducible and CspD has been shown to be stationary-phase inducible. The cspI gene is located at 35.2 min on the E. coli chromosome map, and CspI shows 70, 70, and 79% identity to CspA, CspB, and CspG, respectively. Analyses of cspI-lacZ fusion constructs and the cspI mRNA revealed that cspI is cold shock inducible. The 5'-untranslated region of the cspI mRNA consists of 145 bases and causes a negative effect on cspI expression at 37 degrees C. The cspI mRNA was very unstable at 37 degrees C but was stabilized upon cold shock. Analyses of the CspI protein on two-dimensional gel electrophoresis revealed that CspI production is maximal at or below 15 degrees C. Taking these results together, E. coli possesses a total of four cold shock-inducible proteins in the CspA family. Interestingly, the optimal temperature ranges for their induction are different: CspA induction occurs over the broadest temperature range (30 to 10 degrees C), CspI induction occurs over the narrowest and lowest temperature range (15 to 10 degrees C), and CspB and CspG occurs at temperatures between the above extremes (20 to 10 degrees C). 相似文献