全文获取类型
收费全文 | 22747篇 |
免费 | 2247篇 |
国内免费 | 5篇 |
出版年
2023年 | 89篇 |
2022年 | 201篇 |
2021年 | 428篇 |
2020年 | 277篇 |
2019年 | 401篇 |
2018年 | 448篇 |
2017年 | 431篇 |
2016年 | 784篇 |
2015年 | 1228篇 |
2014年 | 1264篇 |
2013年 | 1544篇 |
2012年 | 1846篇 |
2011年 | 1665篇 |
2010年 | 1173篇 |
2009年 | 1075篇 |
2008年 | 1332篇 |
2007年 | 1326篇 |
2006年 | 1200篇 |
2005年 | 1215篇 |
2004年 | 1144篇 |
2003年 | 1115篇 |
2002年 | 1030篇 |
2001年 | 209篇 |
2000年 | 130篇 |
1999年 | 229篇 |
1998年 | 258篇 |
1997年 | 200篇 |
1996年 | 180篇 |
1995年 | 174篇 |
1994年 | 161篇 |
1993年 | 160篇 |
1992年 | 156篇 |
1991年 | 115篇 |
1990年 | 126篇 |
1989年 | 106篇 |
1988年 | 106篇 |
1987年 | 85篇 |
1986年 | 104篇 |
1985年 | 88篇 |
1984年 | 121篇 |
1983年 | 73篇 |
1982年 | 114篇 |
1981年 | 86篇 |
1980年 | 92篇 |
1979年 | 66篇 |
1978年 | 47篇 |
1977年 | 56篇 |
1976年 | 49篇 |
1975年 | 48篇 |
1974年 | 46篇 |
排序方式: 共有10000条查询结果,搜索用时 312 毫秒
41.
42.
Marie Armani-Tourret Zhicheng Zhou Romain Gasser Isabelle Staropoli Vincent Cantaloube-Ferrieu Yann Benureau Javier Garcia-Perez Mayte Prez-Olmeda Valrie Lorin Bndicte Puissant-Lubrano Lambert Assoumou Constance Delaugerre Jean-Daniel Lelivre Yves Lvy Hugo Mouquet Guillaume Martin-Blondel Jose Alcami Fernando Arenzana-Seisdedos Jacques Izopet Philippe Colin Bernard Lagane 《PLoS pathogens》2021,17(4)
HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses’ receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART. 相似文献
43.
Mathieu Lefèvre Daniel J. Felmlee Marie Parnot Thomas F. Baumert Catherine Schuster 《PloS one》2014,9(4)
Hepatitis C virus (HCV) is a major cause of liver disease worldwide and HCV infection represents a major health problem. HCV associates with host lipoproteins forming host/viral hybrid complexes termed lipoviral particles. Apolipoprotein E (apoE) is a lipoprotein component that interacts with heparan sulfate proteoglycans (HSPG) to mediate hepatic lipoprotein uptake, and may likewise mediate HCV entry. We sought to define the functional regions of apoE with an aim to identify critical apoE binding partners involved in HCV infection. Using adenoviral vectors and siRNA to modulate apoE expression we show a direct correlation of apoE expression and HCV infectivity, whereas no correlation exists with viral protein expression. Mutating the HSPG binding domain (HSPG-BD) of apoE revealed key residues that are critical for mediating HCV infection. Furthermore, a novel synthetic peptide that mimics apoE’s HSPG-BD directly and competitively inhibits HCV infection. Genetic knockdown of the HSPG proteins syndecan (SDC) 1 and 4 revealed that SDC4 principally mediates HCV entry. Our data demonstrate that HCV uses apoE-SDC4 interactions to enter hepatoma cells and establish infection. Targeting apoE-SDC interactions could be an alternative strategy for blocking HCV entry, a critical step in maintaining chronic HCV infection. 相似文献
44.
45.
46.
47.
Pirjo Rajaniemi‐Wacklin Anne Rantala Maria. A. Mugnai Silvia Turicchia Stefano Ventura Jarka Komrkov Liisa Lepist Kaarina Sivonen 《Journal of phycology》2006,42(1):226-232
In this study, the first reported isolates of the genera Snowella and Woronichinia were characterized by 16S rRNA gene sequencing and morphological analysis. Phylogenetic studies and sequences for these genera were not available previously. By botanical criteria, the five isolated strains were identified as Snowella litoralis (Häyrén) Komárek et Hindák Snowella rosea (Snow) Elenkin and Woronichinia naegeliana (Unger) Elenkin. This study underlines the identification of freshly isolated cultures, since the Snowella strains lost the colony structure and were not identifiable after extended laboratory cultivation. In the 16S rRNA gene analysis, the Snowella strains formed a monophyletic cluster, which was most closely related to the Woronichinia strain. Thus, our results show that the morphology of the genera Snowella and Woronichinia was in congruence with their phylogeny, and their phylogeny seems to support the traditional botanical classification of these genera. Furthermore, the genera Snowella and Woronichinia occurred commonly and might occasionally be the most abundant cyanobacterial taxa in mainly oligotrophic and mesotrophic Finnish lakes. Woronichinia occurred frequently and also formed blooms in eutrophic Czech reservoirs. 相似文献
48.
Piet J. van den Hout Theunis Piersma Anne Dekinga Suzanne K. Lubbe G. Henk Visser 《Journal of avian biology》2006,37(5):425-430
To cope with changes in the environment, organisms not only show behavioural but also phenotypic adjustments. This is well established for the digestive tract. Here we present a first case of birds adjusting their flight machinery in response to predation risk. In an indoor experiment, ruddy turnstones Arenaria interpres were subjected to an unpredictable daily appearance of either a raptor or a small gull (as a control). Ruddy turnstones experiencing threat induced by a flying raptor model, longer than after similar passage by the gull model, refrained from feeding after this disturbance. Pectoral muscle mass, but not lean mass, responded in a course of a few days to changes in the perceived threat of predation. Pectoral muscle mass increased after raptor scares. Taking the small increases in body mass into account, pectoral muscle mass was 3.6% higher than aerodynamically predicted for constant flight performance. This demonstrates that perceived risk factors may directly affect organ size. 相似文献
49.
Penicillium citrinum cultures have been germinated on an H2O-based medium, resuspended on a D2O-based medium and treated with [l,2-13C2] acetate. The resulting citrinin (1) has been analysed by2H and13C nuclear magnetic resonance spectroscopy and information about the metabolism of hydrogen in citrinin biosynthesis has been deduced. 相似文献
50.
Jaroslav Votruba Jarmila Pazlarová Milada Dvořáková Kalju Vanatalu Libuše Váchová Marie Strnadová Helena Kučerová Jiří Chaloupka 《Applied microbiology and biotechnology》1987,26(4):373-377
Summary A mathematical model was formulated to describe the kinetics and stoichiometry of growth and proteinase production in Bacillus megaterium. Synthesis of the extracellular proteinase in a batch culture is repressed by amino acids. The specific rate of formation of the enzyme (r
E) can be described by the formula {ie373-1}, where k
2 and k
3 stand for the non-repressible and repressible part of enzyme synthesis respectively, k
S
2 is a repression coefficient and S
2 indicates the concentration of amono acids; the values of k
2 and k
S
2 depend on the composition of the mixture of amino acids. Even in a high concentration, a single amino acid is less effective than a mixture of amino acids. The dependence of the proteinase repression on the concentration of an external amino acid (leucine) follows the same course as its rate of incorporation into proteins, approaching saturation at concentrations higher than 50 M (half saturation approximately 10 M). However, the total uptake of leucine did not exhibit any saturation even at 500 M external concentration.Symbols
X
biomass concentration, g/l
-
E
proteinase concentration, unit/l
-
t
time, h
-
S
1
concentration of glucose, g/l
-
S
2
concentration of amino acids, g/l
-
specific growth rate, l/h
-
rE
specific rate of enzyme production, unit/g/h
-
k
1
growth kinetic constant, l/h
-
k
2
product formation kinetic constant (for non-repressible part of enzyme synthesis), unit/g
-
k
3
product formation kinetic constant (for repressible portion of enzyme synthesis), unit/g
-
k
S
1
saturation constant, g/l
-
k
S
2
repression coefficient for a certain amino acid or amino acids mixture, g/l 相似文献