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991.
Takao Suzuki Minoru Moriya Toshihiro Sakamoto Takuya Suga Hiroyuki Kishino Hidekazu Takahashi Makoto Ishikawa Keita Nagai Yumiko Imai Etsuko Sekino Masahiko Ito Hisashi Iwaasa Akane Ishihara Shigeru Tokita Akio Kanatani Nagaaki Sato Takehiro Fukami 《Bioorganic & medicinal chemistry letters》2009,19(11):3072-3077
Optimization of high-throughput screening hit 1a led to the identification of a novel spiro-piperidine class of melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. Compound 3c was identified as a highly potent and selective MCH-1R antagonist, which has an IC50 value of 0.09 nM at hMCH-1R. The synthesis and structure–activity relationships of the novel spiro-piperidine MCH-1R antagonists are described. 相似文献
992.
Akinori Sato Takuro Arimura Naomasa Makita Taisuke Ishikawa Yoshiyasu Aizawa Hiroya Ushinohama Yoshifusa Aizawa Akinori Kimura 《The Journal of biological chemistry》2009,284(50):35122-35133
Long QT syndrome (LQTS) is a hereditary arrhythmia caused by mutations in genes for cardiac ion channels, including a potassium channel, KvLQT1. Inheritance of LQTS is usually autosomal-dominant, but autosomal-recessive inheritance can be observed in patients with LQTS accompanied by hearing loss. In this study, we investigated the functional alterations caused by KCNQ1 mutations, a deletion (delV595) and a frameshift (P631fs/19), which were identified in compound heterozygous state in two patients with autosomal-recessive LQTS not accompanied by hearing loss. Functional analyses showed that both mutations impaired cell surface expression due to trafficking defects. The mutations severely affected outward potassium currents without apparent dominant negative effects. It was found that delV595 impaired subunit binding, whereas P631fs/19 was retained in endoplasmic reticulum due to the newly added 19-amino acid sequence containing two retention motifs (R633GR and R646LR). This is the first report of novel mechanisms for trafficking abnormality of cardiac ion channels, providing us new insights into the molecular mechanisms of LQTS. 相似文献
993.
Cloning,sequence analysis,and expression of a gene encoding <Emphasis Type="Italic">Chromobacterium</Emphasis> sp. DS-1 cholesterol oxidase 总被引:1,自引:1,他引:0
Noriyuki Doukyu Kanpei Shibata Hiroyasu Ogino Martin Sagermann 《Applied microbiology and biotechnology》2009,82(3):479-490
Chromobacterium sp. strain DS-1 produces an extracellular cholesterol oxidase that is very stable at high temperatures and in the presence
of organic solvents and detergents. In this study, we cloned and sequenced the structural gene encoding the cholesterol oxidase.
The primary translation product was predicted to be 584 amino acid residues. The mature product is composed of 540 amino acid
residues. The amino acid sequence of the product showed significant similarity (53–62%) to the cholesterol oxidases from Burkholderia spp. and Pseudomonas aeruginosa. The DNA fragment corresponding to the mature enzyme was subcloned in the pET-21d(+) expression vector and expressed as an
active product in Escherichia coli. The cholesterol oxidase produced from the recombinant E. coli was purified to homogeneity. The physicochemical properties were similar to those of native enzyme purified from strain DS-1.
K
m and V
max values of the cholesterol oxidase were estimated from Lineweaver–Burk plots. The V
max/K
m ratio of the enzyme was higher than those of commercially available cholesterol oxidases. The circular dichroism spectral
analysis of the recombinant DS-1 enzyme and Burkholderia cepacia ST-200 cholesterol oxidase showed that the conformational stability of the DS-1 enzyme was higher than that of B. cepacia ST-200 enzyme at higher temperatures. 相似文献
994.
Rongsheng Jin Satinder K Singh Shenyan Gu Hiroyasu Furukawa Alexander I Sobolevsky Jie Zhou Yan Jin Eric Gouaux 《The EMBO journal》2009,28(12):1812-1823
Fast excitatory neurotransmission is mediated largely by ionotropic glutamate receptors (iGluRs), tetrameric, ligand‐gated ion channel proteins comprised of three subfamilies, AMPA, kainate and NMDA receptors, with each subfamily sharing a common, modular‐domain architecture. For all receptor subfamilies, active channels are exclusively formed by assemblages of subunits within the same subfamily, a molecular process principally encoded by the amino‐terminal domain (ATD). However, the molecular basis by which the ATD guides subfamily‐specific receptor assembly is not known. Here we show that AMPA receptor GluR1‐ and GluR2‐ATDs form tightly associated dimers and, by the analysis of crystal structures of the GluR2‐ATD, propose mechanisms by which the ATD guides subfamily‐specific receptor assembly. 相似文献
995.
996.
997.
Simon W. Wright Akira Ishikawa Harvey J. Marchant Andrew T. Davidson Rick L. van den Enden Geraldine V. Nash 《Polar Biology》2009,32(5):797-808
Filter fractionated picophytoplankton from Antarctic coastal waters (summer 2001) represented only 7–33% of total phytoplankton,
even though total stocks were low (average Chl a = 0.32 μg l−1, range = 0.13–1.03 μg l−1). Though all cells passed a 2 μm filter, electron microscopy revealed most cells were over 2 μm, principally Parmales, Phaeocystis sp., and small diatoms. CHEMTAX analysis of HPLC pigment data suggested type 8 haptophytes (e.g. Phaeocystis sp. plus Parmales and pelagophytes) contributed 7–58% of picoplanktonic chlorophyll a, type 6 haptophytes (e.g. coccolithophorids) 18–59%, diatoms 0–18% (mostly type 2 diatoms, e.g. Pseudonitzschia sp., 0–15%), prasinophytes 0–17%, with cell fragments of cryptophytes 0–40%, and dinoflagellates 0–11%. Only stocks of type
8 haptophytes and prasinophytes differed significantly due to successional changes. Zeaxanthin concentrations exceeded estimates
from previous cyanobacterial counts and may derive from non-photosynthetic bacteria. 相似文献
998.
Takabayashi A Ishikawa N Obayashi T Ishida S Obokata J Endo T Sato F 《The Plant journal : for cell and molecular biology》2009,57(2):207-219
Chloroplastic NAD(P)H dehydrogenase (NDH) plays a role in cyclic electron flow around photosystem I to produce ATP, especially in adaptation to environmental changes. Although the NDH complex contains 11 subunits that are homologous to NADH:ubiquinone oxidoreductase (complex I; EC 1.6.5.3), recent genetic and biological studies have indicated that NDH also comprises unique subunits. We describe here an in silico approach based on co-expression analysis and phylogenetic profiling that was used to identify 65 genes as potential candidates for NDH subunits. Characterization of 21 Arabidopsis T-DNA insertion mutants among these ndh gene candidates indicated that three novel ndf (NDH-dependent cyclic electron flow) mutants ( ndf1 , ndf2 and ndf4 ) had impaired NDH activity as determined by measurement of chlorophyll fluorescence. The amount of NdhH subunit was greatly decreased in these mutants, suggesting that the loss of NDH activity was caused by a defect in accumulation of the NDH complex. In addition, NDF1, NDF2 and NDF4 proteins co-migrated with the NdhH subunit, as shown by blue native electrophoresis. These results strongly suggest that NDF proteins are novel subunits of the NDH complex. Further analysis revealed that the NDF1 and NDF2 proteins were unstable in the mutants lacking hydrophobic subunits of the NDH complex, but were stable in mutants lacking the hydrophilic subunits, suggesting that NDF1 and NDF2 interact with a hydrophobic sub-complex. NDF4 protein was predicted to possess a redox-active iron–sulfur cluster domain that may be involved in the electron transfer. 相似文献
999.
The first synthesis of the ganglioside LLG-3 tetrasaccharide, which has attractive biological activities as well as a unique structure, is described. A C8-methoxy decorated sialic acid building block was initially prepared and a glycolic acid moiety was then introduced by sialylation. Amide condensation between the sialyl glycolic acid and an amino group at C5 on the sialyllactoside unit afforded the fully protected LLG-3 tetrasaccharide. Finally, the desired tetrasaccharide part of LLG-3 was obtained after careful global deprotection. 相似文献
1000.
Hatsune Makino Masashi Toyoda Kenji Matsumoto Hirohisa Saito Koichiro Nishino Yoshihiro Fukawatase Masakazu Machida Hidenori Akutsu Taro Uyama Yoshitaka Miyagawa Hajime Okita Nobutaka Kiyokawa Takashi Fujino Yuichi Ishikawa Takuro Nakamura Akihiro Umezawa 《Experimental cell research》2009,315(16):2727-2740
POU5F1 (more commonly known as OCT4/3) is one of the stem cell markers, and affects direction of differentiation in embryonic stem cells. To investigate whether cells of mesenchymal origin acquire embryonic phenotypes, we generated human cells of mesodermal origin with overexpression of the chimeric OCT4/3 gene with physiological co-activator EWS (product of the EWSR1 gene), which is driven by the potent EWS promoter by translocation. The cells expressed embryonic stem cell genes such as NANOG, lost mesenchymal phenotypes, and exhibited embryonal stem cell-like alveolar structures when implanted into the subcutaneous tissue of immunodeficient mice. Hierarchical analysis by microchip analysis and cell surface analysis revealed that the cells are subcategorized into the group of human embryonic stem cells and embryonal carcinoma cells. These results imply that cells of mesenchymal origin can be traced back to cells of embryonic phenotype by the OCT4/3 gene in collaboration with the potent cis-regulatory element and the fused co-activator. The cells generated in this study with overexpression of chimeric OCT4/3 provide us with insight into cell plasticity involving OCT4/3 that is essential for embryonic cell maintenance, and the complexity required for changing cellular identity. 相似文献