全文获取类型
收费全文 | 1388篇 |
免费 | 89篇 |
国内免费 | 2篇 |
出版年
2022年 | 8篇 |
2021年 | 19篇 |
2020年 | 10篇 |
2019年 | 8篇 |
2018年 | 14篇 |
2017年 | 17篇 |
2016年 | 35篇 |
2015年 | 49篇 |
2014年 | 61篇 |
2013年 | 82篇 |
2012年 | 111篇 |
2011年 | 107篇 |
2010年 | 68篇 |
2009年 | 51篇 |
2008年 | 82篇 |
2007年 | 81篇 |
2006年 | 90篇 |
2005年 | 87篇 |
2004年 | 97篇 |
2003年 | 72篇 |
2002年 | 54篇 |
2001年 | 5篇 |
1999年 | 13篇 |
1998年 | 15篇 |
1997年 | 10篇 |
1996年 | 9篇 |
1995年 | 11篇 |
1994年 | 14篇 |
1993年 | 11篇 |
1991年 | 7篇 |
1990年 | 6篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1982年 | 7篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1975年 | 4篇 |
1974年 | 5篇 |
1971年 | 5篇 |
1962年 | 5篇 |
1935年 | 4篇 |
1934年 | 3篇 |
1912年 | 4篇 |
排序方式: 共有1479条查询结果,搜索用时 15 毫秒
121.
Background
Working in healthcare is often considered a risk factor for influenza; however, this risk has not been quantified. We aimed to systematically review evidence describing the annual incidence of influenza among healthy adults and healthcare workers (HCWs).Methods and Findings
We searched OVID MEDLINE (1950 to 2010), EMBASE (1947 to 2010) and reference lists of identified articles. Observational studies or randomized trials reporting full season or annual influenza infection rates for healthy, working age adult subjects and HCWs were included. Influenza infection was defined as a four-fold rise in antibody titer, or positive viral culture or polymerase chain reaction.From 24,707 citations, 29 studies covering 97 influenza seasons with 58,245 study participants were included. Pooled influenza incidence rates (IR) (95% confidence intervals (CI)) per 100 HCWs per season and corresponding incidence rate ratios (IRR) (95% CI) as compared to healthy adults were as follows. All infections: IR 18.7 (95% CI, 15.8 to 22.1), IRR 3.4 (95% CI, 1.2 to 5.7) in unvaccinated HCWs; IR 6.5 (95% CI, 4.6 to 9.1), IRR 5.4 (95% CI, 2.8 to 8.0) in vaccinated HCWs. Symptomatic infections: IR 7.5 (95% CI, 4.9 to 11.7), IRR 1.5 (95% CI, 0.4 to 2.5) in unvaccinated HCWs, IR 4.8 (95% CI, 3.2 to 7.2), IRR 1.6 (95% CI, 0.5 to 2.7) in vaccinated HCWs.Conclusions
Compared to adults working in non-healthcare settings, HCWs are at significantly higher risk of influenza. 相似文献122.
A common founder for amyotrophic lateral sclerosis type 8 (ALS8) in the Brazilian population 总被引:3,自引:0,他引:3
The P56S mutation in the VAPB gene causes ALS8. Eight families, comprising more than 1,500 individuals of whom about 200 are affected, are now known to carry this mutation. Seven are of Portuguese–Brazilian ancestry and one of African–Brazilian ancestry. Haplotype analysis shows a common founder for all families regardless of ancestry, with a founding event 23 generations ago (95% CI 13–39), consistent with the Portuguese colonization of Brazil.Agnes L. Nishimura, Ammar Al-Chalabi contributed equally to this work 相似文献
123.
Crystal structure of a secreted insect ferritin reveals a symmetrical arrangement of heavy and light chains 总被引:2,自引:0,他引:2
Hamburger AE West AP Hamburger ZA Hamburger P Bjorkman PJ 《Journal of molecular biology》2005,349(3):558-569
Ferritins are iron storage proteins made of 24 subunits forming a hollow spherical shell. Vertebrate ferritins contain varying ratios of heavy (H) and light (L) chains; however, known ferritin structures include only one type of chain and have octahedral symmetry. Here, we report the 1.9A structure of a secreted insect ferritin from Trichoplusia ni, which reveals equal numbers of H and L chains arranged with tetrahedral symmetry. The H/L-chain interface includes complementary features responsible for ordered assembly of the subunits. The H chain contains a ferroxidase active site resembling that of vertebrate H chains with an endogenous, bound iron atom. The L chain lacks the residues that form a putative iron core nucleation site in vertebrate L chains. Instead, a possible nucleation site is observed at the L chain 3-fold pore. The structure also reveals inter- and intrasubunit disulfide bonds, mostly in the extended N-terminal regions unique to insect ferritins. The symmetrical arrangement of H and L chains and the disulfide crosslinks reflect adaptations of insect ferritin to its role as a secreted protein. 相似文献
124.
Walldén K Ruzzenente B Rinaldo-Matthis A Bianchi V Nordlund P 《Structure (London, England : 1993)》2005,13(7):1081-1088
The human mitochondrial deoxyribonucleotidase catalyzes the dephosphorylation of thymidine and deoxyuridine monophosphates and participates in the regulation of the dTTP pool in mitochondria. We present seven structures of the inactive D41N variant of this enzyme in complex with thymidine 3'-monophosphate, thymidine 5'-monophosphate, deoxyuridine 5'-monophosphate, uridine 5'-monophosphate, deoxyguanosine 5'-monophosphate, uridine 2'-monophosphate, and the 5'-monophosphate of the nucleoside analog 3'-deoxy 2'3'-didehydrothymidine, and we draw conclusions about the substrate specificity based on comparisons with enzyme activities. We show that the enzyme's specificity for the deoxyribo form of nucleoside 5'-monophosphates is due to Ile-133, Phe-49, and Phe-102, which surround the 2' position of the sugar and cause an energetically unfavorable environment for the 2'-hydroxyl group of ribonucleoside 5'-monophosphates. The close binding of the 3'-hydroxyl group of nucleoside 5'-monophosphates to the enzyme indicates that nucleoside analog drugs that are substituted with a bulky group at this position will not be good substrates for this enzyme. 相似文献
125.
We present evidence that ubiquitination controls sorting of the ABC-transporter Ste6 in the early endocytic pathway. The intracellular distribution of Ste6 variants with reduced ubiquitination was examined. In contrast to wild-type Ste6, which was mainly localized to internal structures, these variants accumulated at the cell surface in a polar manner. When endocytic recycling was blocked by Ypt6 inactivation, the ubiquitination deficient variants were trapped inside the cell. This indicates that the polar distribution is maintained dynamically through endocytic recycling and localized exocytosis ("kinetic polarization"). Ste6 does not appear to recycle through late endosomes, because recycling was not blocked in class E vps (vacuolar protein sorting) mutants (Deltavps4, Deltavps27), which are affected in late endosome function and in the retromer mutant Deltavps35. Instead, recycling was partially affected in the sorting nexin mutant Deltasnx4, which serves as an indication that Ste6 recycles through early endosomes. Enhanced recycling of wild-type Ste6 was observed in class D vps mutants (Deltapep12, Deltavps8, and Deltavps21). The identification of putative recycling signals in Ste6 suggests that recycling is a signal-mediated process. Endocytic recycling and localized exocytosis could be important for Ste6 polarization during the mating process. 相似文献
126.
Kovács L Csanádi A Kiss E Miczak A 《Acta microbiologica et immunologica Hungarica》2005,52(3-4):363-371
Rv0802c acetyltransferase is a mycobacterial RNase E-associated protein. 6His and FLAG-tagged acetyltransferase was cloned from Mycobacterium tuberculosis H37Rv, expressed in Escherichia coli and partially purified. It is a 25 kDa protein showing a modest sequence homology with other acetyltransferases. The R-X-X-G-X-G sequence for acetyl-coenzyme A recognition and binding can be found in the molecule. 相似文献
127.
Agnes?E.?AsagbraEmail author Abiodun?I.?Sanni Olusola?B.?Oyewole 《World journal of microbiology & biotechnology》2005,21(2):107-114
The ability of Streptomyces sp. OXCI, S. rimosus NRRL B2659, S. rimosus NRRL B2234, S. alboflavus NRRL B1273 S. aureofaciens NRRL B2183 and S. vendagensis ATCC 25507 to produce tetracycline using some local agricultural wastes as solid state media, were assessed. The wastes employed include peanut (groundnut) shells, corncob, corn pomace and cassava peels. Bacillus subtilis ATCC 6633 was used to assay antimicrobial activity. All the strains produced tetracycline in a solid-state fermentation process containing peanut (groundnut) as the carbohydrate source. Streptomyces sp. OXC1 had the highest ability for tetracycline production with peanut shells as the substrate in solid fermentation (13.18 mg/g), followed by S. vendagensis ATCC 25507 (11.08 mg/g), S.rimosus NRRL B1679 (8.46 mg/g), S. alboflavus NRRL B1273 (7.59 mg/g), S. rimosus NRRL B2234 (6.37 mg/g), S. aureofaciens NRRL B2183 (4.27 mg/g). Peanut (groundnut) shells were the most effective substrate (4.36 mg/g) followed by corncob (2.64 mg/g), cassava peels (2.16 mg/g) and corn pomace (1.99 mg/g). The composition of the peanut (groundnut) shell medium optimal for tetracycline production were peanut shells 100 g, organic nitrogen (peanut meal) 10 g, (NH 4)2 SO4 1 g, KH2 PO 4 0.5 g, CaCO3 > 0.5 g, NaCl 0.5 g, MgSO4 · 7H2 O 0.5 g, soluble starch 10 g, peanut oil 0.25 ml with initial moisture content of 65–68%, and initial pH 5.3–6.3. Substrate (1 g dry weight) was inoculated with 1.0 × 10 8 conidia per ml and incubated at 28–31 °C for 5–7 days, producing 13.18 mg/g of total tetracycline. Tetracycline detection started on day 3 and attained its maximum level on day 5. 相似文献
128.
dos Santos JI Takeda AA Marchi-Salvador DP Soares AM Fontes MR 《Protein and peptide letters》2005,12(8):819-822
BnSP-7 and BnSP-6, two Lys49-phospholipase A2 isolated from Bothrops neuwiedi pauloensis snake venom, were co-crystallized with alpha-tocopherol and X-ray diffraction data were collected for both complexes (2.2 and 2.6 A). A new "alternative" quaternary conformation for these two complexes compared with all other dimeric Lys49-PLA2 has been observed. 相似文献
129.
Bogácsi-Szabó E Kalmár T Csányi B Tömöry G Czibula A Priskin K Horváth F Downes CS Raskó I 《Human biology; an international record of research》2005,77(5):639-662
The Cumanians were originally Asian pastoral nomads who in the 13th century migrated to Hungary. We have examined mitochondrial DNA from members of the earliest Cumanian population in Hungary from two archeologically well-documented excavations and from 74 modern Hungarians from different rural locations in Hungary. Haplogroups were defined based on HVS I sequences and examinations of haplogroup-associated polymorphic sites of the protein coding region and of HVS II. To exclude contamination, some ancient DNA samples were cloned. A database was created from previously published mtDNA HVS I sequences (representing 2,615 individuals from different Asian and European populations) and 74 modem Hungarian sequences from the present study. This database was used to determine the relationships between the ancient Cumanians, modern Hungarians, and Eurasian populations and to estimate the genetic distances between these populations. We attempted to deduce the genetic trace of the migration of Cumanians. This study is the first ancient DNA characterization of an eastern pastoral nomad population that migrated into Europe. The results indicate that, while still possessing a Central Asian steppe culture, the Cumanians received a large admixture of maternal genes from more westerly populations before arriving in Hungary. A similar dilution of genetic, but not cultural, factors may have accompanied the settlement of other Asian nomads in Europe. 相似文献
130.
Wrigley JD Schurov I Nunn EJ Martin AC Clarke EE Ellis S Bonnert TP Shearman MS Beher D 《The Journal of biological chemistry》2005,280(13):12523-12535
Presenilins appear to form the active center of gamma-secretase but require the presence of the integral membrane proteins nicastrin, anterior pharynx defective 1, and presenilin enhancer 2 for catalytic function. We have simultaneously overexpressed all of these polypeptides, and we demonstrate functional assembly of the enzyme complex, a substantial increase in enzyme activity, and binding of all components to a transition state analogue gamma-secretase inhibitor. Co-localization of all components can be observed in the Golgi compartment, and further trafficking of the individual constituents seems to be dependent on functional assembly. Apart from its catalytic function, gamma-secretase appears to play a role in the trafficking of the beta-amyloid precursor protein, which was changed upon reconstitution of the enzyme but unaffected by pharmacological inhibition. Because the relative molecular mass and stoichiometry of the active enzyme complex remain elusive, we performed size exclusion chromatography of solubilized gamma-secretase, which yielded evidence of a tetrameric form of the complex, yet almost completely abolished enzyme activity. Gamma-secretase activity was reconstituted upon addition of an independent size exclusion chromatography fraction of lower molecular mass and nonproteinaceous nature, which could be replaced by a brain lipid extract. The same treatment was able to restore enzyme activity after immunoaffinity purification of the gamma-secretase complex, demonstrating that lipids play a key role in preserving the catalytic activity of this protease. Furthermore, these data show that it is important to discriminate between intact, inactive gamma-secretase complexes and the active form of the enzyme, indicating the care that must be taken in the study of gamma-secretase. 相似文献