全文获取类型
收费全文 | 4242篇 |
免费 | 380篇 |
国内免费 | 3篇 |
出版年
2023年 | 28篇 |
2022年 | 56篇 |
2021年 | 132篇 |
2020年 | 79篇 |
2019年 | 93篇 |
2018年 | 116篇 |
2017年 | 106篇 |
2016年 | 173篇 |
2015年 | 313篇 |
2014年 | 283篇 |
2013年 | 275篇 |
2012年 | 456篇 |
2011年 | 367篇 |
2010年 | 235篇 |
2009年 | 188篇 |
2008年 | 272篇 |
2007年 | 255篇 |
2006年 | 200篇 |
2005年 | 196篇 |
2004年 | 139篇 |
2003年 | 133篇 |
2002年 | 113篇 |
2001年 | 26篇 |
2000年 | 27篇 |
1999年 | 20篇 |
1998年 | 28篇 |
1997年 | 11篇 |
1996年 | 12篇 |
1995年 | 13篇 |
1994年 | 14篇 |
1993年 | 12篇 |
1992年 | 22篇 |
1991年 | 16篇 |
1990年 | 15篇 |
1988年 | 13篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 9篇 |
1984年 | 16篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 12篇 |
1979年 | 12篇 |
1975年 | 10篇 |
1974年 | 12篇 |
1973年 | 9篇 |
1972年 | 7篇 |
1970年 | 7篇 |
1969年 | 7篇 |
1968年 | 7篇 |
排序方式: 共有4625条查询结果,搜索用时 140 毫秒
101.
Eva Hell Christian G. Giske Kjell Hultenby Kristina Gemzell Danielsson Giovanna Marchini 《Current microbiology》2013,67(6):712-717
Staphylococcus epidermidis, a human commensal, is an important opportunistic, biofilm-forming pathogen and the main cause of late onset sepsis in preterm infants, worldwide. In this study we describe the characteristics of S. epidermidis strains causing late onset (>72 h) bloodstream infection in preterm infants and skin isolates from healthy newborns. Attachment and biofilm formation capability were analyzed in microtiter plates and with transmission electron microscopy (TEM). Clonal relationship among strains was studied with pulsed-field gel electrophoresis. Antimicrobial susceptibility testing was performed, as well as the detection of biofilm-associated genes and of the invasiveness marker IS256 with polymerase chain reaction. Blood and skin isolates had similar attachment and biofilm-forming capabilities and biofilm formation was not related to the presence of specific genes. Filament-like membrane structures were seen by TEM early in the attachment close to the device surface, both in blood and skin strains. Nine of the ten blood isolates contained the IS256 and were also resistant to methicillin and gentamicin in contrast to skin strains. S. epidermidis strains causing bloodstream infection in preterm infants exhibit higher antibiotic resistance and are provided with an invasive genetic equipment compared to skin commensal strains. Adhesion capability to a device surface seems to involve bacterial membrane filaments. 相似文献
102.
Taner Cavlar Tobias Deimling Andrea Ablasser Karl‐Peter Hopfner Veit Hornung 《The EMBO journal》2013,32(10):1440-1450
Extensive research on antiviral small molecules starting in the early 1970s has led to the identification of 10‐carboxymethyl‐9‐acridanone (CMA) as a potent type I interferon (IFN) inducer. Up to date, the mode of action of this antiviral molecule has remained elusive. Here we demonstrate that CMA mediates a cell‐intrinsic type I IFN response, depending on the ER‐resident protein STING. CMA directly binds to STING and triggers a strong antiviral response through the TBK1/IRF3 route. Interestingly, while CMA displays extraordinary activity in phosphorylating IRF3 in the murine system, CMA fails to activate human cells that are otherwise responsive to STING ligands. This failure to activate human STING can be ascribed to its inability to bind to the C‐terminal ligand‐binding domain of human STING. Crystallographic studies show that two CMA molecules bind to the central Cyclic diguanylate ( c‐diGMP)‐binding pocket of the STING dimer and fold the lid region in a fashion similar, but partially distinct, to c‐diGMP. Altogether, these results provide novel insight into ligand‐sensing properties of STING and, furthermore, unravel unexpected species‐specific differences of this innate sensor. 相似文献
103.
104.
105.
Carmen F. Ludwig Florian Ullrich Lilia Leisle Tobias Stauber Thomas J. Jentsch 《The Journal of biological chemistry》2013,288(40):28611-28619
CLC anion transporters form dimers that function either as Cl− channels or as electrogenic Cl−/H+ exchangers. CLC channels display two different types of “gates,” “protopore” gates that open and close the two pores of a CLC dimer independently of each other and common gates that act on both pores simultaneously. ClC-7/Ostm1 is a lysosomal 2Cl−/1H+ exchanger that is slowly activated by depolarization. This gating process is drastically accelerated by many CLCN7 mutations underlying human osteopetrosis. Making use of some of these mutants, we now investigate whether slow voltage activation of plasma membrane-targeted ClC-7/Ostm1 involves protopore or common gates. Voltage activation of wild-type ClC-7 subunits was accelerated by co-expressing an excess of ClC-7 subunits carrying an accelerating mutation together with a point mutation rendering these subunits transport-deficient. Conversely, voltage activation of a fast ClC-7 mutant could be slowed by co-expressing an excess of a transport-deficient mutant. These effects did not depend on whether the accelerating mutation localized to the transmembrane part or to cytoplasmic cystathionine-β-synthase (CBS) domains of ClC-7. Combining accelerating mutations in the same subunit did not speed up gating further. No currents were observed when ClC-7 was truncated after the last intramembrane helix. Currents and slow gating were restored when the C terminus was co-expressed by itself or fused to the C terminus of the β-subunit Ostm1. We conclude that common gating underlies the slow voltage activation of ClC-7. It depends on the CBS domain-containing C terminus that does not require covalent binding to the membrane domain of ClC-7. 相似文献
106.
107.
108.
Sjannie Lefevre Tobias Wang Do Thi Thanh Huong Nguyen Thanh Phuong Mark Bayley 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2013,183(2):215-221
Though air-breathing has probably evolved mainly as a response to hypoxia, it may provide an important oxygen supplement when metabolism is elevated, as for example during swimming. Due to the increased travelling distance involved when an air-breathing fish swims to and from the surface, and the increased drag when the surface is breached, it can be proposed that air-breathing results in a rise in the apparent cost of transport. In order to investigate this hypothesis, it is necessary to use a fish that is able to swim equally well with and without access to air. The striped catfish Pangasianodon hypophthalmus has been shown to have a sufficiently high capacity for aquatic oxygen uptake in normoxia, to allow for such a comparison. Here, we measured the partitioning of oxygen uptake ( $ \dot{M}{\text{O}}_{2} $ ) during swimming and recovery, and calculated the apparent cost of transport with and without access to air, under normoxic conditions. Aerial $ \dot{M}{\text{O}}_{2} $ constituted 25–40 % of the total $ \dot{M}{\text{O}}_{2} $ during swimming and less than 15 % during recovery. The net cost of transport was 25 % lower in fish that did not air-breathe compared to fish that did, showing that the cost of surfacing can be substantial. This is the first study to measure partitioning in an air-breathing fish during swimming at velocities close to the critical swimming speed. 相似文献
109.
Kevin?N.?LalandEmail author John?Odling-Smee William?Hoppitt Tobias?Uller 《Biology & philosophy》2013,28(5):793-810
We are grateful to the commentators for taking the time to respond to our article. Too many interesting and important points have been raised for us to tackle them all in this response, and so in the below we have sought to draw out the major themes. These include problems with both the term ‘ultimate causation’ and the proximate-ultimate causation dichotomy more generally, clarification of the meaning of reciprocal causation, discussion of issues related to the nature of development and phenotypic plasticity and their roles in evolution, and consideration of the need for an extended evolutionary synthesis. 相似文献
110.
Tobias Heck Greta Faccio Michael Richter Linda Thöny-Meyer 《Applied microbiology and biotechnology》2013,97(2):461-475
The process of protein crosslinking comprises the chemical, enzymatic, or chemoenzymatic formation of new covalent bonds between polypeptides. This allows (1) the site-directed coupling of proteins with distinct properties and (2) the de novo assembly of polymeric protein networks. Transferases, hydrolases, and oxidoreductases can be employed as catalysts for the synthesis of crosslinked proteins, thereby complementing chemical crosslinking strategies. Here, we review enzymatic approaches that are used for protein crosslinking at the industrial level or have shown promising potential in investigations on the lab-scale. We illustrate the underlying mechanisms of crosslink formation and point out the roles of the enzymes in their natural environments. Additionally, we discuss advantages and drawbacks of the enzyme-based crosslinking strategies and their potential for different applications. 相似文献