全文获取类型
收费全文 | 1891篇 |
免费 | 185篇 |
国内免费 | 3篇 |
出版年
2023年 | 9篇 |
2022年 | 13篇 |
2021年 | 45篇 |
2020年 | 12篇 |
2019年 | 40篇 |
2018年 | 31篇 |
2017年 | 25篇 |
2016年 | 61篇 |
2015年 | 98篇 |
2014年 | 113篇 |
2013年 | 123篇 |
2012年 | 169篇 |
2011年 | 169篇 |
2010年 | 111篇 |
2009年 | 100篇 |
2008年 | 124篇 |
2007年 | 123篇 |
2006年 | 121篇 |
2005年 | 129篇 |
2004年 | 113篇 |
2003年 | 100篇 |
2002年 | 88篇 |
2001年 | 21篇 |
2000年 | 12篇 |
1999年 | 18篇 |
1998年 | 16篇 |
1997年 | 9篇 |
1996年 | 11篇 |
1995年 | 11篇 |
1994年 | 7篇 |
1993年 | 8篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有2079条查询结果,搜索用时 31 毫秒
1.
Thorsten Thye Genevieve Scarisbrick Edmund N. L. Browne Margaret Amanua Chinbuah John Gyapong Ivy Osei Ellis Owusu-Dabo Stefan Niemann Sabine Rüsch-Gerdes Christian G. Meyer Rolf D. Horstmann 《PloS one》2009,4(7)
The gene of Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4), a negative regulator of T lymphocytes, contains a single-nucleotide polymorphism (SNP) at position +6230A->G (ct60A->G), which has been found associated with several autoimmune diseases and appears to reduce T-cell inhibitory activity. In Ghana, West Africa, we compared the frequencies of CTLA4 +6230 A/G and 6 haplotype-tagging SNPs in 2010 smear-positive, HIV-negative patients with pulmonary tuberculosis (TB) and 2346 controls matched for age, gender and ethnicity. We found no difference in allele frequencies between cases and controls. However, +6230A and a distinct CTLA4 haplotype and a diplotype comprising the +6230A allele were significantly less frequent among cases with large opacities in chest radiographs compared to those with small ones (Pcorrected [cor] = 0.002, Pcor = 0.00045, P = 0.0005, respectively). This finding suggests that an increased T-cell activity associated with the CTLA4 +6230G allele contributes to pathology rather than to protection in pulmonary TB. 相似文献
2.
Eugénie Bassères Giuseppe Coppotelli Thorsten Pfirrmann Jens B. Andersen Maria Masucci Teresa Frisan 《Cellular microbiology》2010,12(11):1622-1633
Invasion of eukaryotic target cells by pathogenic bacteria requires extensive remodelling of the membrane and actin cytoskeleton. Here we show that the remodelling process is regulated by the ubiquitin C‐terminal hydrolase UCH‐L1 that promotes the invasion of epithelial cells by Listeria monocytogenes and Salmonella enterica. Knockdown of UCH‐L1 reduced the uptake of both bacteria, while expression of the catalytically active enzyme promoted efficient internalization in the UCH‐L1‐negative HeLa cell line. The entry of L. monocytogenes involves binding to the receptor tyrosine kinase Met, which leads to receptor phosphorylation and ubiquitination. UCH‐L1 controls the early membrane‐associated events of this triggering cascade since knockdown was associated with altered phosphorylation of the c‐cbl docking site on Tyr1003, reduced ubiquitination of the receptor and altered activation of downstream ERK1/2‐ and AKT‐dependent signalling in response to the natural ligand Hepatocyte Growth Factor (HGF). The regulation of cytoskeleton dynamics was further confirmed by the induction of actin stress fibres in HeLa expressing the active enzyme but not the catalytic mutant UCH‐L1C90S. These findings highlight a previously unrecognized involvement of the ubiquitin cycle in bacterial entry. UCH‐L1 is highly expressed in malignant cells that may therefore be particularly susceptible to invasion by bacteria‐based drug delivery systems. 相似文献
3.
Autonomous DNA replication in human cells is affected by the size and the source of the DNA. 总被引:31,自引:13,他引:18
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We previously developed short-term and long-term assays for autonomous replication of DNA in human cells. This study addresses the requirements for replication in these assays. Sixty-two random human genomic fragments ranging in size from 1 to 21 kb were cloned in a prokaryotic vector and tested for their replication ability in the short-term assay. We found a positive correlation between replication strength and fragment length, indicating that large size is favored for efficient autonomous replication in human cells. All large fragments replicated efficiently, suggesting that signals which can direct the initiation of DNA replication in human cells are either very abundant or have a low degree of sequence specificity. Similar results were obtained in the long-term assay. We also used the same assays to test in human cells a random series of fragments derived from Escherichia coli chromosomal DNA. The bacterial fragments supported replication less efficiently than the human fragments in the short-term and long-term assays. This result suggests that while the sequence signals involved in replication in human cells are found frequently in human DNA, they are uncommon in bacterial DNA. 相似文献
4.
Hartmut Böhm Hans-Georg Heinzel Hans Scharstein Gernot Wendler 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1991,169(6):671-683
The wind-orientated walk of carrion beetles Necrophorus humator F. was analysed under closed-loop conditions with a walking compensator and under openloop conditions with a paired tread wheel (Fig. 1).
相似文献
1. | On the walking compensator an animal runs stable courses with a preferred direction relative to an air current (velocity =; 100 cm/s, Fig. 2B-D). A change in the air-current direction causes a corresponding adjustment of the mean walking direction (Fig. 3). Such course adjustment works best for changes in the air-current direction by an absolute value of 90° (Table 2). |
2. | Under closed-loop conditions the animal shows deviations of less than ± 45° around its preferred direction relative to the wind (Fig. 2B-D). The characteristic curve which describes the animal's angular velocity as a function of the animal's walking direction relative to the air-current stimulus is therefore revealed only in this angular range (Fig. 3, top). |
3. | Under open-loop conditions, however, complete characteristic curves can be obtained because the animal's walking reaction in response to any given angle of air-current stimulus is measurable on the paired tread wheel (Fig. 4). The characteristic curves are approximately sinusoidal functions. They can either show a shift parallel to the ordinale by a superimposed direction-independent constant angular velocity alone or, at the same time, they can independently exhibit an angular shift along the abscissa (Fig. 5). |
4. | The walking tracks straighten with increasing air-current velocity (Fig. 6A, insets), i.e. the animal more rapidly compensates deviations from a preferred course. This corresponds to higher amplitudes of the characterisic curve and steeper slopes at the negative zero-crossing point under open- as well as under closed-loop conditions (Fig. 6). |
5. | Walking in an air-current field can be explained by a model of the course control system using a feedback loop (Fig. 7). This model operates according to a sinusoidal characteristic function on which is superimposed a Gaussian white noise process of angular velocity which is independent of walking direction. The model produces realistic walking tracks in an air-current field (Fig. 8). |
5.
Thorsten Ahl 《Hydrobiologia》1988,170(1):35-44
The role of phosphorus in the eutrophication of lakes and marine coastal areas has created a need of more information on the size of a virgin background supply of phosphorus.The general pollution of the atmosphere has resulted in an increased amount of anthropogenic phosphorus in air masses over remote ocean areas in the Northern Hemisphere. As a consequence this applies also to remote land areas, where the phosphorus deposition of about 5 kg P km-2 a-1 may seem to be 2–3 times the virgin phosphorus deposition.The present background drainage basin yield of phosphorus is also elevated due to a general eutrophication of the terrestrial ecosystem. The background supply varies due to several factors of which drainage basin size, geology and vegetation are discussed. Background yields apparently have a range from 3–10 kg P km-2 a-1. 相似文献
6.
ban operon of bacteriophage P1. Mutational analysis of the c1 repressor-controlled operator 总被引:6,自引:0,他引:6
The repressor of bacteriophage P1, encoded by the c1 gene, represses the phage lytic functions and is responsible for maintaining the P1 prophage in the lysogenic state. The c1 repressor interacts with at least 11 binding sites or operators widely scattered over the P1 genome. From these operators, a 17 base-pair asymmetric consensus sequence, ATTGCTCTAATAAATTT, was derived. Here, we show that the operator, Op72 of the P1ban operon consists of two overlapping 17 base-pair sequences a and b forming an incomplete palindrome. Op72a matches the consensus sequence, whereas Op72b contains two mismatches. The evidence is based on the sequence analysis of 27 operator mutants constitutive for ban expression. They were identified as single-base substitutions at positions 2 to 10 of Op72a (26 mutants) and at position 8 of Op72b (one mutant). We conclude from gel retardation and footprinting studies that two repressor molecules bind to the operator and that positions 4, 5 and 7 to 10 of the operator play an essential role in repressor recognition. 相似文献
7.
Hans -Georg Heinzel Hartmut Böhm 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1989,164(6):775-786
The wind-orientation of carrion beetles (Necrophorus humator F.) was studied by use of a locomotion-compensator.
相似文献
1. | Beetles walking on a horizontal surface for periods of several minutes in a dark environment without an air current and other orientational stimuli seldom keep straight paths. They walk along individually different circular paths (Fig. 1). The mean walking speed is 5.6±1.0 cm/s. The mean of the angular velocity reaches maximally 25 °/s for individual beetles (mean angular velocity of the analysed population of 152 beetles: 1.9±9.3 °/s). The distribution of the mean walking directions of the population shows that the beetles display no preference for one direction (Fig. 3 A). The instantaneous value of the individual angular velocity is independent of the instantaneous walking direction. |
2. | During exposure to an air current the individual beetles keep straight and stable courses with any orientation relative to the direction of air flow (Fig. 4). The mean walking directions of 76 individuals point in all directions but there is a weak preference of windward tracks (Fig. 3B). |
3. | Wind orientated walking starts at a threshold wind velocity of about 5 cm/s (Fig. 6). The walking tracks straighten with increasing air current velocity. This leads to a narrowing of the distribution of the instantaneous walking directions around the preferred walking direction (Fig. 7C). This narrowing is due to an increase in the slope of the characteristic curve (angular velocity as a function of walking direction) of the wind-orientation system. |
4. | Twenty percent of the beetles show a spontaneous change of their anemotactic course during walks of 5 min duration. Neither the time of the change, its position on the track or the direction of the new course are predictable. There is, however, a slight preference for 90±20° changes in the walking direction (Fig. 8). |
5. | The antennae (Fig. 9) act as the only sense organs responsible for the wind orientation. The capability for wind orientated walks is lost after ablation of both flagella (Fig. 10). |
8.
Three species which contain both gyrophoric and lecanoric acids and possess perithecioid ascomata are recognized in the genusDiploschistes. D. badius andD. gyrophoricus are described as new, whileD. subcupreus is reduced to synonymy withD. sticticus. Two species occur in the southern hemisphere, whileD. badius is found in N. America. 相似文献
9.
10.
Leaves of Kalanchoë daigremontiana Hamet et Perr. at a photon flux density (PFD) above 220 mol·m–2s–1 (400–700 nm) or at leaf temperatures above 27.0 °C showed a rapid loss of rhythmicity, and a more or less pronounced damping-out of the endogenous circadian rhythm of CO2 exchange under continuous illumination. This rhythm was reinitiated after reduction of the PFD by 90–120 mol·m–2·s–1 or reduction of leaf temperature by 3.5–11.0 °C under otherwise unchanged external conditions. The reduction in the magnitude of the external control parameter of the Crassulacean acid metabolism (CAM) rhythm (i.e. PFD or leaf temperature) set the phase of the new rhythm. The maxima of CO2 uptake occurred about 5, 28, 51, 75 h after the reduction. Simulations with a CAM model under comparable conditions showed a similar behaviour. The influence of temperature on the endogenous CAM rhythm observed in K. daigremontiana in vivo could be simulated by incorporating into the model temperature-dependent switch modes for passive efflux of malate from the vacuole to the cytoplasm. Thus, the model indicates that tonoplast function plays an important role in regulation of the endogenous CAM rhythm in K. daigremontiana.Abbreviations CAM
Crassulacean acid metabolism
- PAR
photosynthetically active radiation
- PFD
photon flux density
This work was supported by a grant to F.B. and U.L. from Teilprojekt B5 in the Sonderforschungsbereich 199 of the Deutsche Forschungsgemeinschaft (Bonn, Germany) and by a grant to T. E. E. G. from the Sudienstiftung des deutschen Volkes (Bonn, Germany). Erika Ball is thanked for processing of time-course data for the analysis of Fourier spectra. 相似文献