全文获取类型
收费全文 | 6112篇 |
免费 | 542篇 |
国内免费 | 339篇 |
专业分类
6993篇 |
出版年
2024年 | 18篇 |
2023年 | 207篇 |
2022年 | 294篇 |
2021年 | 329篇 |
2020年 | 300篇 |
2019年 | 355篇 |
2018年 | 336篇 |
2017年 | 279篇 |
2016年 | 223篇 |
2015年 | 239篇 |
2014年 | 360篇 |
2013年 | 393篇 |
2012年 | 253篇 |
2011年 | 354篇 |
2010年 | 241篇 |
2009年 | 259篇 |
2008年 | 287篇 |
2007年 | 269篇 |
2006年 | 244篇 |
2005年 | 223篇 |
2004年 | 199篇 |
2003年 | 185篇 |
2002年 | 137篇 |
2001年 | 78篇 |
2000年 | 90篇 |
1999年 | 69篇 |
1998年 | 53篇 |
1997年 | 52篇 |
1996年 | 35篇 |
1995年 | 34篇 |
1994年 | 35篇 |
1993年 | 27篇 |
1992年 | 18篇 |
1991年 | 19篇 |
1989年 | 13篇 |
1988年 | 11篇 |
1987年 | 23篇 |
1986年 | 17篇 |
1985年 | 35篇 |
1984年 | 52篇 |
1983年 | 46篇 |
1982年 | 44篇 |
1981年 | 44篇 |
1980年 | 32篇 |
1979年 | 36篇 |
1978年 | 43篇 |
1977年 | 27篇 |
1976年 | 14篇 |
1975年 | 17篇 |
1974年 | 20篇 |
排序方式: 共有6993条查询结果,搜索用时 10 毫秒
31.
Rogelio Zamilpa Elizabeth F. Lopez Ying Ann Chiao Qiuxia Dai Gladys P. Escobar Kevin Hakala Susan T. Weintraub Merry L. Lindsey 《Proteomics》2010,10(11):2214-2223
Matrix metalloproteinase‐9 (MMP‐9) deletion has been shown to improve remodeling of the left ventricle post‐myocardial infarction (MI), but the mechanisms to explain this improvement have not been fully elucidated. MMP‐9 has a broad range of in vitro substrates, but relevant in vivo substrates are incompletely defined. Accordingly, we evaluated the infarct regions of wild‐type (wt) and MMP‐9 null (null) mice using a proteomic strategy. Wt and null groups showed similar infarct sizes (48±3 in wt and 45±3% in null), indicating that both groups received an equal injury stimulus. Left ventricle infarct tissue was homogenized and analyzed by 2‐DE and MS. Of 31 spot intensity differences, the intensities of 9 spots were higher and 22 spots were lower in null mice compared to wt (all p<0.05). Several extracellular matrix proteins were identified in these spots by MS, including fibronectin, tenascin‐C, thrombospondin‐1, and laminin. Fibronectin was observed on the gels at a lower than expected molecular weight in the wt group, which suggested substrate cleavage, and the lower molecular weight spot was observed at lower intensity in the MMP‐9 null group, which suggested cleavage by MMP‐9. Immunoblotting confirmed the presence of fibronectin cleavage products in the wt samples and lower levels in the absence of MMP‐9. In conclusion, examining infarct tissue from wt and MMP‐9 null mice by proteomic analysis provides a powerful and unique method to identify in vivo candidate MMP substrates. 相似文献
32.
Steven E. J. Bell M. Anthony McKervey Darren Fayne Patrick Kane Dermot Diamond 《Journal of molecular modeling》1998,4(1):44-52
Molecular mechanics calculations have been used to model the geometries of the complexes of Group I metal ions with calix[n]arenes (n = 4,5). A simple procedure in which the calixarene atoms are assigned partial charges on the basis of AM1 calculations and the metal ions are allowed to bind electrostatically to the calixarenes produces surprising good results when the resulting structures are compared to known crystallographic data on the complexes. Encapsulated solvent molecules and/or counterions can be included in the calculations and, indeed, are necessary to reproduce the X-ray data. Electronic Supplementary Material available. 相似文献
33.
Silurian calcispheres (Calcitarcha) of Gotland (Sweden): Comparisons with calcareous dinoflagellates
Scanning electron microscope examinations of polished and etched surfaces of sediments from the Silurian carbonate platform of Gotland, Sweden, revealed the presence of numerous, morphologically diverse “calcispheres” (Calcitarcha). Some of these spherical calcareous microfossils display wall structures that are surprisingly similar to those of calcareous dinoflagellate cysts. In analogy to the interpretation of the biological affinities of Palaeozoic acritarchs as cysts of organisms that might have been the ancestors of organic-walled dinoflagellates, the Calcitarcha from Gotland can be compared and may possibly be related to organisms that may have been the ancestors of calcareous cyst-producing dinoflagellates that so far have not been observed before the Late Jurassic. 相似文献
34.
Laura ConteBernard L. Trumpower Vincenzo Zara 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(1):91-101
The yeast cytochrome bc1 complex, a component of the mitochondrial respiratory chain, is composed of ten distinct protein subunits. In the assembly of the bc1 complex, some ancillary proteins, such as the chaperone Bcs1p, are actively involved. The deletion of the nuclear gene encoding this chaperone caused the arrest of the bc1 assembly and the formation of a functionally inactive bc1 core structure of about 500-kDa. This immature bc1 core structure could represent, on the one hand, a true assembly intermediate or, on the other hand, a degradation product and/or an incorrect product of assembly. The experiments here reported show that the gradual expression of Bcs1p in the yeast strain lacking this protein was progressively able to rescue the bc1 core structure leading to the formation of the functional homodimeric bc1 complex. Following Bcs1p expression, the mature bc1 complex was also progressively converted into two supercomplexes with the cytochrome c oxidase complex. The capability of restoring the bc1 complex and the supercomplexes was also possessed by the mutated yeast R81C Bcsp1. Notably, in the human ortholog BCS1L, the corresponding point mutation (R45C) was instead the cause of a severe bc1 complex deficiency. Differently from the yeast R81C Bcs1p, two other mutated Bcs1p's (K192P and F401I) were unable to recover the bc1 core structure in yeast. This study identifies for the first time a productive assembly intermediate of the yeast bc1 complex and gives new insights into the molecular mechanisms involved in the last steps of bc1 assembly. 相似文献
35.
Rodini CO Batista AC Dionísio TJ Santos CF Cunha FQ Lara VS 《Journal of molecular histology》2008,39(3):275-282
The immunopathologic and inflammatory mechanisms involved in periodontal disease (PD) include the participation of host resident,
inflammatory cells and chemical mediators. Metalloproteinases (MMPs) and nitric oxide (NO) play essential role in extracellular
matrix turnover of periodontal tissue destruction. In this study, by means of RT-PCR through semi-quantitative densitometric
scanning methods, the expression of MMPs -2 and -9 and inducible NO synthase (iNOS) was temporally and spatially investigated
during the destructive mechanisms of experimentally induced PD in rats. Samples from different periods were microscopically
analyzed and compared with the contralateral side (control). Our results showed significant expression of MMP-9 and iNOS in
tissues affected by PD, as compared with controls, three days after PD induction, simultaneously with the beginning of alveolar
bone loss. At 7 days post induction, only the MMP-9 mRNA presented a significantly higher expression, as compared with the
respective controls. Thus, in the rat ligature-induced PD, MMP-9 and iNOS might importantly participate in the early stages
of the disease, including inflammatory cell migration, tissue destruction and alveolar bone resorption. Also, we may suggest
that the exuberant presence of PMNs may be related to the important expression of iNOS and MMP-9 found at 3 days post induction. 相似文献
36.
The significance of impairment of proteasome activity in PC12 cells was examined in connection with nitrative/nitrosative stress and apoptotic cell death. Treatment of differentiated PC12 cells with MG132, a proteasome inhibitor, elicited a dose- and time-dependent increase in neuronal nitric oxide synthase (nNOS) protein levels, decreased cell viability, and increased cytotoxicity. Viability and cytotoxicity were ameliorated by L-NAME (a broad NOS inhibitor). Nitric oxide/peroxynitrite formation was increased upon treatment of PC12 cells with MG132 and decreased upon treatment with the combination of MG132 and 7-NI (a specific inhibitor of nNOS). The decreases in cell viability appeared to be effected by an activation of JNK and its effect on mitochondrial Bcl-xL phosphorylation. These effects are strengthened by the activation of caspase-9 along with increased caspase-3 activity upon treatment of PC12 cells with MG132. These results suggest that impairment of proteasome activity and consequent increases in nNOS levels lead to a nitrative stress that involves the coordinated response of JNK cytosolic signaling and mitochondrion-driven apoptotic pathways. 相似文献
37.
Pesenti ME Spinelli S Bezirard V Briand L Pernollet JC Tegoni M Cambillau C 《Journal of molecular biology》2008,380(1):158-169
The behavior of insects and their perception of their surroundings are driven, in a large part, by odorants and pheromones. This is especially true for social insects, such as the honey bee, where the queen controls the development and the caste status of the other individuals. Pheromone perception is a complex phenomenon relying on a cascade of recognition events, initiated in antennae by pheromone recognition by a pheromone-binding protein and finishing with signal transduction at the axon membrane level. With to the objective of deciphering this initial step, we have determined the structures of the bee antennal pheromone-binding protein (ASP1) in the apo form and in complex with the main component of the queen mandibular pheromonal mixture, 9-keto-2(E)-decenoic acid (9-ODA) and with nonpheromonal components. In the apo protein, the C terminus obstructs the binding site. In contrast, ASP1 complexes have different open conformations, depending on the ligand shape, leading to different volumes of the binding cavity. The binding site integrity depends on the C terminus (111-119) conformation, which involves the interplay of two factors; i.e. the presence of a ligand and a low pH. Ligand binding to ASP1 is favored by low pH, opposite to what is observed with other pheromone-binding proteins, such as those of Bombyx mori and Anopheles gambiae. 相似文献
38.
Ewelina Minta Pawel Kafarski Jean Martinez Valérie Rolland 《Journal of peptide science》2008,14(3):267-277
ω‐AGA IVB is an important lead structure when considering the design of effectors of glutamate release inducting P/Q‐type calcium channels. The best route to achieve the analogues possessing the three‐dimensional arrangement corresponding to the native binding loop was the introduction of constraint by ring formation via side chain to side chain lactamization for suitably protected Lys and Glu residues. Since tryptophane residue located at position 14 of this neuropeptide has been suggested as essential for binding, analogues in which this amino acid was replaced by aza‐tryptophane and alanine were synthesized. The synthesis was carried out on various acid‐labile resins (BARLOS chlorotrityl, Rink amide, PEG‐based or Wang resins), by Fmoc strategy. In this paper, we describe optimization of the peptide cyclization with various protecting groups, and on resin or in solution cyclization experimental parameters. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
39.
Reduced fertility of female mice lacking CD81 总被引:7,自引:0,他引:7
Rubinstein E Ziyyat A Prenant M Wrobel E Wolf JP Levy S Le Naour F Boucheix C 《Developmental biology》2006,290(2):351-358
In somatic cells, the tetraspanins CD81 and CD9 associate with each other, with additional tetraspanins and with non-tetraspanin molecules to form proteolipidic complexes. Here we show that CD81 is expressed on the surface of oocytes where it associates with tetraspanin-enriched membrane structures. A major CD9 and CD81 partner, CD9P-1, is also expressed by oocytes. Deletion of CD81 gene in mice results in a 40% reduction of female fertility. In vitro insemination indicated that this infertility is due to a deficiency of oocytes to fuse with sperm. While the fertility of CD9-/- mice is severely but not completely impaired, double knock-out CD9-/- CD81-/- mice were completely infertile indicating that CD9 and CD81 play complementary roles in sperm-egg fusion. Finally, a fraction of CD9 was transferred from CD81-/- oocytes to sperm present in the perivitelline space indicating that the defect of fusion of CD81-/- oocytes does not result from an impaired initial gamete interaction. 相似文献
40.