全文获取类型
收费全文 | 2403篇 |
免费 | 153篇 |
国内免费 | 1篇 |
专业分类
2557篇 |
出版年
2023年 | 3篇 |
2022年 | 8篇 |
2021年 | 31篇 |
2020年 | 14篇 |
2019年 | 19篇 |
2018年 | 29篇 |
2017年 | 30篇 |
2016年 | 64篇 |
2015年 | 97篇 |
2014年 | 100篇 |
2013年 | 140篇 |
2012年 | 216篇 |
2011年 | 167篇 |
2010年 | 95篇 |
2009年 | 112篇 |
2008年 | 160篇 |
2007年 | 160篇 |
2006年 | 132篇 |
2005年 | 146篇 |
2004年 | 129篇 |
2003年 | 104篇 |
2002年 | 126篇 |
2001年 | 33篇 |
2000年 | 21篇 |
1999年 | 31篇 |
1998年 | 35篇 |
1997年 | 29篇 |
1996年 | 37篇 |
1995年 | 25篇 |
1994年 | 22篇 |
1993年 | 29篇 |
1992年 | 26篇 |
1991年 | 18篇 |
1990年 | 19篇 |
1989年 | 16篇 |
1988年 | 15篇 |
1987年 | 8篇 |
1986年 | 16篇 |
1985年 | 18篇 |
1984年 | 14篇 |
1983年 | 12篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 8篇 |
1977年 | 4篇 |
1976年 | 7篇 |
1973年 | 1篇 |
1866年 | 1篇 |
排序方式: 共有2557条查询结果,搜索用时 15 毫秒
91.
Definition of a short region of XPG necessary for TFIIH interaction and stable recruitment to sites of UV damage 下载免费PDF全文
Thorel F Constantinou A Dunand-Sauthier I Nouspikel T Lalle P Raams A Jaspers NG Vermeulen W Shivji MK Wood RD Clarkson SG 《Molecular and cellular biology》2004,24(24):10670-10680
XPG is the human endonuclease that cuts 3' to DNA lesions during nucleotide excision repair. Missense mutations in XPG can lead to xeroderma pigmentosum (XP), whereas truncated or unstable XPG proteins cause Cockayne syndrome (CS), normally yielding life spans of <7 years. One XP-G individual who had advanced XP/CS symptoms at 28 years has been identified. The genetic, biochemical, and cellular defects in this remarkable case provide insight into the onset of XP and CS, and they reveal a previously unrecognized property of XPG. Both of this individual's XPG alleles produce a severely truncated protein, but an infrequent alternative splice generates an XPG protein lacking seven internal amino acids, which can account for his very slight cellular UV resistance. Deletion of XPG amino acids 225 to 231 does not abolish structure-specific endonuclease activity. Instead, this region is essential for interaction with TFIIH and for the stable recruitment of XPG to sites of local UV damage after the prior recruitment of TFIIH. These results define a new functional domain of XPG, and they demonstrate that recruitment of DNA repair proteins to sites of damage does not necessarily lead to productive repair reactions. This observation has potential implications that extend beyond nucleotide excision repair. 相似文献
92.
Five typhloplanoids from the Australian East Coast are reported, three of them new to science. Two taxa are members of Promesostomidae: Vauclusia conica n.g. n.sp., characterised by a cone-shaped stylet, the presence of a female bursa and a very long, partially-swollen female duct; Brinkmanniella australiensis n.sp. has a funnel-shaped stylet with a smooth distal tip. Pilamonila bimascula n.g. n.sp. is a representative of the Solenopharyngidae, characterised by a stylet within a cirrus. The known species found are Ceratopera axi and Ptychopera scutulifer. 相似文献
93.
Following incubation of mesophilic methanogenic floccular sludge from a lab-scale upflow anaerobic sludge bed reactor used to treat cattle manure wastewater, a stable 5-aminosalicylate-degrading enrichment culture was obtained. Subsequently, a Citrobacter freundii strain, WA1, was isolated from the 5-aminosalicylate-degrading methanogenic consortium. The methanogenic enrichment culture degraded 5-aminosalicylate completely to CH4, CO2 and NH4
+, while C. freundii strain WA1 reduced 5-aminosalicylate with simultaneous deamination to 2-hydroxybenzyl alcohol during anaerobic growth with electron donors such as pyruvate, glucose or serine. When grown on pyruvate, C. freundii WA1 converted 3-aminobenzoate to benzyl alcohol and also reduced benzaldehyde to benzyl alcohol. Pyruvate was fermented to acetate, CO2, H2 and small amounts of lactate, succinate and formate. Less lactate (30%) was produced from pyruvate when C. freundii WA1 grew with 5-aminosalicylate as co-substrate. 相似文献
94.
Draaijers LJ Tempelman FR Botman YA Tuinebreijer WE Middelkoop E Kreis RW van Zuijlen PP 《Plastic and reconstructive surgery》2004,113(7):1960-5; discussion 1966-7
At present, various scar assessment scales are available, but not one has been shown to be reliable, consistent, feasible, and valid at the same time. Furthermore, the existing scar assessment scales appear to attach little weight to the opinion of the patient. The newly developed Patient and Observer Scar Assessment Scale consists of two numeric scales: the Patient Scar Assessment Scale (patient scale) and the Observer Scar Assessment Scale (observer scale). The patient and observer scales have to be completed by the patient and the observer, respectively. The patient scale's consistency and the observer scale's consistency, reliability, and feasibility were tested. For the Vancouver Scar Scale, which is the most frequently used scar assessment scale at present, the same statistical measurements were examined and the results of the observer scale and the Vancouver scale were compared. The concurrent validity of the observer scale was tested with a correlation to the Vancouver scale. Furthermore, the authors examined which specific characteristics significantly influence the general opinion of the patient and the observers on the scar areas. Four independent observers have each used the observer scale and the Vancouver scale to assess 49 burn scar areas of 3 x 3 cm belonging to 20 different patients. Subsequently, the patients completed the patient scale for their scar areas. The (internal) consistency of both the patient and the observer scales was acceptable (Cronbach's alpha, 0.76 and 0.69, respectively), whereas the consistency of the Vancouver scale appeared not to be acceptable (alpha, 0.49). The reliability of the observer scale completed by a single observer was acceptable (r = 0.73). The reliability of the Vancouver scale completed by a single observer was lower (r = 0.69). The observer scale showed better agreement than the Vancouver scale because the coefficient of variation was lower (18 percent and 22 percent, respectively). The concurrent validity of the observer scale in relation to the Vancouver scale is high (r = 0.89, p < 0.001). Linear regression of the general opinions on scars of the observer and the patient showed that the observer's opinion is influenced by vascularization, thickness, pigmentation, and relief, whereas the patient's opinion is mainly influenced by itching and the thickness of the scar. Such an impact of itching and thickness of the scar on the patient's opinion is an important and novel finding. The Patient and Observer Scar Assessment Scale offers a suitable, reliable, and complete scar evaluation tool. 相似文献
95.
Cytochromes b561 (cyts b561) constitute a family of eukaryotic membrane proteins, catalysing ascorbate (Asc)-mediated trans-membrane electron transport, and hence likely involved in Asc regeneration. A class of proteins (DoH-CB) has been identified in plants and animals, containing the cyt b561 electron-transport domain (CB), combined with the catecholamine-binding regulatory domain of dopamine-beta-hydroxylase (DoH). A mammalian DoH-CB protein was previously reported to function as a cell-derived growth factor receptor (SDR2). We have performed an in silico analysis on DoH-CB proteins from Arabidopsis thaliana and demonstrate that structural features of both CB and DoH domains are well conserved. The combination of both domains may have evolved from a functional interaction between a cyt b561 and a DoH-containing protein, illustrating the so-called "Rosetta Stone" evolutionary principle, and this hypothesis is supported by sequence comparisons. DoH-CB proteins form a newly identified group of proteins, likely to play a key role in catecholamine action in plants. It is suggested that these proteins may function as trans-membrane electron shuttles, possibly regulated by catecholamines. The role and action of catecholamines in plants is poorly documented, but it is clear that they are involved in many aspects of growth and development. Whether the DoH-CB proteins functionally interact with Asc, as is the case for cyts b561, remains to be determined. 相似文献
96.
A software tool, Sweet Substitute, is described, which assists tandem mass spectrometry (MS/MS)-based glycosylation characterization from within a tryptic digest. The algorithm creates a virtual nanoelectrospray-quadrupole time-of-flight style-MS/MS spectrum of any user-defined N-linked glycan structure. An empirical peak height modeling routine is implemented in the program. By comparing the theoretical MS/MS data with the deconvoluted and deisotoped experimental MS/MS data, the user is able to quickly assess whether a proposed candidate oligosaccharide structure is a plausible one. 相似文献
97.
Designing new materials from wheat protein 总被引:4,自引:0,他引:4
Woerdeman DL Veraverbeke WS Parnas RS Johnson D Delcour JA Verpoest I Plummer CJ 《Biomacromolecules》2004,5(4):1262-1269
We recently discovered that wheat gluten could be formed into a tough, plasticlike substance when thiol-terminated, star-branched molecules are incorporated directly into the protein structure. This discovery offers the exciting possibility of developing biodegradable high-performance engineering plastics and composites from renewable resources that are competitive with their synthetic counterparts. Wheat gluten powder is available at a cost of less than dollars 0.5/lb, so if processing costs can be controlled, an inexpensive alternative to synthetic polymers may be possible. In the present work, we demonstrate the ability to toughen an otherwise brittle protein-based material by increasing the yield stress and strain-to-failure, without compromising stiffness. Water absorption results suggest that the cross-link density of the polymer is increased by the presence of the thiol-terminated, star-branched additive in the protein. Size-exclusion high performance liquid chromatography data of molded tri-thiol-modified gluten are consistent with that of a polymer that has been further cross-linked when compared directly with unmodified gluten, handled under identical conditions. Remarkably, the mechanical properties of our gluten formulations stored in ambient conditions were found to improve with time. 相似文献
98.
The aim of this study was to gain insight into the factors that affect the permeation of volatiles through starch films. These films were obtained by casting gelatinized starch/water/glycerol mixtures. The films were dried and conditioned under different conditions (temperature and relative humidity) resulting in films that vary in the degree of starch crystallinity and glycerol and water content. The permeation of two model volatiles (carvone and diacetyl) at 20 degrees C and at 30, 60, or 90% relative humidity (RH) was analyzed gravimetrically. Further, the solubility of the two model compounds (under conditions where the permeation experiments were carried out) was determined. From the obtained permeation and solubility data, the diffusion coefficients of these compounds in the different starch films were calculated. The crystallinity in the starch films increased with increasing water content of the films during preparation. The water content of the resulting films in turn increased with increasing glycerol and when the films were exposed to a higher RH during drying or conditioning. For films with the same composition, the flux for diacetyl was greater than for carvone. The solubilities of diacetyl and carvone were slightly dependent on the properties of the films. It was found that with increasing starch crystallinity the diffusion coefficient for both compounds decreases, which is probably due to the impermeability of starch crystallites. Interestingly, in films with about the same extent of crystallinity, the diffusion can be described with the free volume model, with water and glycerol determining the amount of free volume. 相似文献
99.
Two technetium-99m-labeled cholecystokinin-8 (CCK8) peptides for scintigraphic imaging of CCK receptors 总被引:2,自引:0,他引:2
Laverman P Béhé M Oyen WJ Willems PH Corstens FH Behr TM Boerman OC 《Bioconjugate chemistry》2004,15(3):561-568
A broad spectrum of radiolabeled peptides with high affinity for receptors expressed on tumor cells is currently under preclinical and clinical investigation for scintigraphic imaging and radionuclide therapy. The present paper evaluates two (99m)Tc-labeled forms of the C-terminal octapeptide of cholecystokinin (CCK8): sulfated (s)CCK8, with high affinity for CCK1 and CCK2 receptors, and nonsulfated (ns)CCK8, with high affinity for CCK2 receptors but low affinity for CCK1 receptors. Peptides were conjugated with the bifunctional chelator N-hydroxysuccinimidyl hydrazino niconitate (s-HYNIC). (99m)Tc-labeling, performed in the presence of nicotinic acid and tricine, was highly efficient (approximately 95%) and yielded products with a high specific activity (approximately 700 Ci/mmol) and good stability (approximately 5% release of radiolabel during 16 h incubation in phosphate buffered saline at 37 degrees C). Chinese hamster ovary cells stably expressing the CCK1 receptor (CHO-CCK1 cells) internalized approximately 3% of added (99m)Tc-sCCK8 per confluent well during 2 h at 37 degrees C. Internalization was effectively blocked by excess unlabeled sCCK8. CHO-CCK1 cells did not internalize (99m)Tc-nsCCK8. Displacement of (99m)Tc-sCCK8 and -nsCCK8 by unlabeled CCK-8 (performed at 0 degrees C to prevent internalization) revealed 50% inhibitory concentrations (IC(50)) of 8 nM and >1 microM, respectively. CHO-CCK2 cells internalized approximately 25% and approximately 5% of added (99m)Tc-sCCK8 and -nsCCK8, respectively. In both cases internalization was blocked by excess unlabeled peptide. IC(50) values for the displacement of (99m)Tc-sCCK8 and -nsCCK8 were 3 nM and 10 nM, respectively. CHO-CCK1 cell-derived tumors present in one flank of athymic mice accumulated 2.0% of injected (99m)Tc-sCCK8 per gram tissue at 1 h postinjection. This value decreased to 0.6% following coinjection with excess unlabeled peptide. Uptake of (99m)Tc-nsCCK8 was low (0.2%) and not did change by excess unlabeled peptide (0.3%). Accumulation of (99m)Tc-sCCK8 and -nsCCK8 by CHO-CCK2 cell-derived tumors (present in the other flank) amounted to 4.2% and 0.6%, respectively. In both cases uptake was significantly reduced by excess unlabeled peptide to 1.0% and 0.4% for sCCK8 and nsCCK8, respectively. Accumulation of (99m)Tc-sCCK8 was also high in pancreas (11.7%), stomach (2.0%), and kidney (2.1%), whereas uptake of (99m)Tc-nsCCK8 was high in stomach (0.7%) and kidney (1.4%). Both radiolabeled peptides showed a rapid blood clearance. In conclusion, these data show that CCK8 analogues can be efficiently labeled with (99m)Tc using s-HYNIC as chelator and nicotinic acid/tricine as coligand system without compromising receptor binding. Furthermore, the present study demonstrates that CCK1 tumors hardly accumulate (99m)Tc-nsCCK8, CCK2 tumors accumulate 2 times more (99m)Tc-sCCK8 than CCK1 tumors, and CCK2 tumors accumulate 15 times more (99m)Tc-sCCK8 than (99m)Tc-nsCCK8. Although accumulation in some nontarget organs was also higher with (99m)Tc-sCCK8, this may not reflect the human situation due to a different receptor expression pattern in humans as compared to mice. Therefore, further studies are warranted to investigate the possible use of (99m)Tc-sCCK8 for scintigraphic imaging of CCK receptor-positive tumors in humans. 相似文献
100.
Lubberts E van den Bersselaar L Oppers-Walgreen B Schwarzenberger P Coenen-de Roo CJ Kolls JK Joosten LA van den Berg WB 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(5):2655-2662
IL-17 is a T cell-derived proinflammatory cytokine in experimental arthritis and is a stimulator of osteoclastogenesis in vitro. In this study, we report the effects of IL-17 overexpression (AdIL-17) in the knee joint of type II collagen-immunized mice on bone erosion and synovial receptor activator of NF-kappa B ligand (RANKL)/receptor activator of NF-kappa B/osteoprotegerin (OPG) expression. Local IL-17 promoted osteoclastic bone destruction, which was accompanied with marked tartrate-resistant acid phosphatase activity at sites of bone erosion in cortical, subchondral, and trabecular bone. Accelerated expression of RANKL and its receptor, receptor activator of NF-kappa B, was found in the synovial infiltrate and at sites of focal bone erosion, using specific immunohistochemistry. Interestingly, AdIL-17 not only enhanced RANKL expression but also strongly up-regulated the RANKL/OPG ratio in the synovium. Comparison of arthritic mice from the AdIL-17 collagen-induced arthritis group with full-blown collagen-arthritic mice having similar clinical scores for joint inflammation revealed lower RANKL/OPG ratio and tartrate-resistant acid phosphatase activity in the latter group. Interestingly, systemic OPG treatment prevented joint damage induced by local AdIL-17 gene transfer in type II collagen-immunized mice. These findings suggest T cell IL-17 to be an important inducer of RANKL expression leading to loss of the RANKL/OPG balance, stimulating osteoclastogenesis and bone erosion in arthritis. 相似文献