全文获取类型
收费全文 | 10408篇 |
免费 | 1015篇 |
国内免费 | 11篇 |
专业分类
11434篇 |
出版年
2021年 | 123篇 |
2019年 | 92篇 |
2018年 | 84篇 |
2017年 | 85篇 |
2016年 | 146篇 |
2015年 | 299篇 |
2014年 | 310篇 |
2013年 | 438篇 |
2012年 | 620篇 |
2011年 | 581篇 |
2010年 | 428篇 |
2009年 | 364篇 |
2008年 | 551篇 |
2007年 | 600篇 |
2006年 | 533篇 |
2005年 | 613篇 |
2004年 | 624篇 |
2003年 | 598篇 |
2002年 | 554篇 |
2001年 | 110篇 |
2000年 | 77篇 |
1999年 | 134篇 |
1998年 | 184篇 |
1997年 | 108篇 |
1996年 | 120篇 |
1995年 | 120篇 |
1994年 | 116篇 |
1993年 | 98篇 |
1992年 | 116篇 |
1991年 | 92篇 |
1990年 | 97篇 |
1989年 | 87篇 |
1988年 | 95篇 |
1987年 | 85篇 |
1986年 | 81篇 |
1985年 | 100篇 |
1984年 | 133篇 |
1983年 | 108篇 |
1982年 | 137篇 |
1981年 | 148篇 |
1980年 | 123篇 |
1979年 | 78篇 |
1978年 | 100篇 |
1977年 | 87篇 |
1976年 | 87篇 |
1975年 | 88篇 |
1974年 | 85篇 |
1973年 | 96篇 |
1972年 | 55篇 |
1971年 | 53篇 |
排序方式: 共有10000条查询结果,搜索用时 10 毫秒
151.
Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: involvement of host proteins TSG101 and VPS-4 下载免费PDF全文
Licata JM Simpson-Holley M Wright NT Han Z Paragas J Harty RN 《Journal of virology》2003,77(3):1812-1819
The VP40 protein of Ebola virus can bud from mammalian cells in the form of lipid-bound, virus-like particles (VLPs), and late budding domains (L-domains) are conserved motifs (PTAP, PPxY, or YxxL; where "x" is any amino acid) that facilitate the budding of VP40-containing VLPs. VP40 is unique in that potential overlapping L-domains with the sequences PTAP and PPEY are present at amino acids 7 to 13 of VP40 (PTAPPEY). L-domains are thought to function by interacting with specific cellular proteins, such as the ubiquitin ligase Nedd4, and a component of the vacuolar protein sorting (vps) pathway, tsg101. Mutational analysis of the PTAPPEY sequence of VP40 was performed to understand further the contribution of each individual motif in promoting VP40 budding. In addition, the contribution of tsg101 and a second member of the vps pathway, vps4, in facilitating budding was addressed. Our results indicate that (i) both the PTAP and PPEY motifs contribute to efficient budding of VP40-containing VLPs; (ii) PTAP and PPEY can function as L-domains when separated and moved from the N terminus (amino acid position 7) to the C terminus (amino acid position 316) of full-length VP40; (iii) A VP40-PTAP/tsg101 interaction recruits tsg101 into budding VLPs; (iv) a VP40-PTAP/tsg101 interaction recruits VP40 into lipid raft microdomains; and (v) a dominant-negative mutant of vps4 (E228Q), but not wild-type vps4, significantly inhibited the budding of Ebola virus (Zaire). These results provide important insights into the complex interplay between viral and host proteins during the late stages of Ebola virus budding. 相似文献
152.
Cohn RD van Erp C Habashi JP Soleimani AA Klein EC Lisi MT Gamradt M ap Rhys CM Holm TM Loeys BL Ramirez F Judge DP Ward CW Dietz HC 《Nature medicine》2007,13(2):204-210
Skeletal muscle has the ability to achieve rapid repair in response to injury or disease. Many individuals with Marfan syndrome (MFS), caused by a deficiency of extracellular fibrillin-1, exhibit myopathy and often are unable to increase muscle mass despite physical exercise. Evidence suggests that selected manifestations of MFS reflect excessive signaling by transforming growth factor (TGF)-beta (refs. 2,3). TGF-beta is a known inhibitor of terminal differentiation of cultured myoblasts; however, the functional contribution of TGF-beta signaling to disease pathogenesis in various inherited myopathic states in vivo remains unknown. Here we show that increased TGF-beta activity leads to failed muscle regeneration in fibrillin-1-deficient mice. Systemic antagonism of TGF-beta through administration of TGF-beta-neutralizing antibody or the angiotensin II type 1 receptor blocker losartan normalizes muscle architecture, repair and function in vivo. Moreover, we show TGF-beta-induced failure of muscle regeneration and a similar therapeutic response in a dystrophin-deficient mouse model of Duchenne muscular dystrophy. 相似文献
153.
Diversification and biogeographic history of the Western Palearctic freshwater flatworm genus Schmidtea (Tricladida: Dugesiidae), with a redescription of Schmidtea nova 下载免费PDF全文
Laia Leria Ronald Sluys Marta Riutort 《Journal of Zoological Systematics and Evolutionary Research》2018,56(3):335-351
The freshwater flatworm genus Schmidtea is endemic in the Western Palearctic region, where it is represented by only four species, thus contrasting with the high species diversity of the closely related genus Dugesia within Europe. Although containing an important model species in developmental and regeneration research, viz. Schmidtea mediterranea, no evolutionary studies on the genus Schmidtea have been undertaken. For the first time, we present a well‐resolved molecular phylogenetic tree of the four species of the genus, inferred on the basis of two molecular markers, and provide also the first detailed morphological account of Schmidtea nova. The phylogenetic tree generated corroborates an earlier speciation hypothesis based on karyological data and points to chromosomal rearrangements as the main drivers of speciation in this genus. The high genetic divergence between the four species, in combination with previous dating studies and their current geographic distribution, suggests that Schmidtea could have originated in Laurasia but lost most of its diversity during the Oligocene. Thus, its present distribution pattern may be the result of the expansion of three of its four relictual species over Europe, probably after the Pleistocene glaciations. Our detailed morphological study of S. nova revealed that it shows a number of remarkable features: interconnected testis follicles, parovaria, an ejaculatory duct exiting into the primary as well as the secondary seminal vesicle by means of a nipple, and the wall of the distal section of the ejaculatory duct being sclerotic or chitinized. 相似文献
154.
155.
Replacement of the P1 amino acid of human immunodeficiency virus type 1 Gag processing sites can inhibit or enhance the rate of cleavage by the viral protease 下载免费PDF全文
Processing of the human immunodeficiency virus type 1 (HIV-1) Gag precursor is highly regulated, with differential rates of cleavage at the five major processing sites to give characteristic processing intermediates. We examined the role of the P1 amino acid in determining the rate of cleavage at each of these five sites by using libraries of mutants generated by site-directed mutagenesis. Between 12 and 17 substitution mutants were tested at each P1 position in Gag, using recombinant HIV-1 protease (PR) in an in vitro processing reaction of radiolabeled Gag substrate. There were three sites in Gag (MA/CA, CA/p2, NC/p1) where one or more substitutions mediated enhanced rates of cleavage, with an enhancement greater than 60-fold in the case of NC/p1. For the other two sites (p2/NC, p1/p6), the wild-type amino acid conferred optimal cleavage. The order of the relative rates of cleavage with the P1 amino acids Tyr, Met, and Leu suggests that processing sites can be placed into two groups and that the two groups are defined by the size of the P1' amino acid. These results point to a trans effect between the P1 and P1' amino acids that is likely to be a major determinant of the rate of cleavage at the individual sites and therefore also a determinant of the ordered cleavage of the Gag precursor. 相似文献
156.
OBJECTIVE: To demonstrate the utility of fine needle aspiration biopsy (FNAB) in radiofrequency ablation (RFA) of suspected metastatic tumors at various sites. STUDY DESIGN: Eighteen patients referred for RFA underwent 21 aspirations prior to the procedure. A radiologist performed the FNAB and RFA with radiographic guidance. On-site preliminary evaluation of Diff-Quik-stained smears were followed with Papanicolaou staining. A final diagnosis was rendered and compared to the preliminary diagnosis. RESULTS: Liver was aspirated in 17 cases, lung in 3 cases and pubic bone in 1. Fifteen aspirates were deemed on site as positive or suspicious for malignancy. A preliminary, on-site diagnosis of benign was given in one case and adequate with deferment for review of all slides in four others. One FNAB was unsatisfactory. All but one (patient with benign diagnosis) then immediately proceeded to RFA of the lesion. After review of additional slides, the final diagnosis confirmed metastatic adenocarcinoma in 16, hepatocellular carcinoma in 2 and metastatic squamous cell carcinoma in 1. One FNAB yielded benign hepatocytes, and one was unsatisfactory. CONCLUSION: FNAB is an accurate, safe and rapid method of confirming disease in patients just prior to undergoing RFA. 相似文献
157.
Effect of Estuarine Sediment pH and Oxidation-Reduction Potential on Microbial Hydrocarbon Degradation 总被引:5,自引:9,他引:5 下载免费PDF全文
Microbial mineralization rates of two petroleum hydrocarbons, as affected by pH and oxidation-reduction potential, were determined in a Barataria Bay, Louisiana, sediment using 14C-labeled hydrocarbons. Hydrocarbon mineralization rates were inferred from the activity of respired 14CO2. Sediment pH and oxidation-reduction potential were important factors in governing the population of hydrocarbon-degrading microorganisms in the sediment and subsequent mineralization rates. Highest mineralization rates occurred at pH 8.0, and the lowest occurred at pH 5.0. At all pH levels mineralization decreased with decreasing oxidation-reduction potential (i.e., increasing sediment anaerobiosis). Generally, mineralization rates for octadecane were greater than those for naphthalene. Aerobic microorganisms in the oxidized sediment were more capable of degrading hydrocarbons than anaerobic microorganisms in reduced sediment of the same pH. 相似文献
158.
159.
Coburn RF 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,112(11):1949-1955
Recent findings that heme oxygenase-1 can be induced by oxidative stress and inflammation in many different cellular systems, and that carbon monoxide (CO) produced as a by-product of this enzyme is a signaling molecule, have generated a major research area with hundreds of studies published over the last few years. The measurement of expired CO concentration has been used in humans as a biomarker of induced heme oxygenase resulting from inflammation or oxidative stress, but a precise method of measuring endogenous CO production that can be easily used to study patients is needed. The present study describes such a method. The described method allows calculation of the rate of heme catabolism with a precision of ±2 μmol/h, ~10% of the mean normal rate in subjects used in this investigation. This method, which is subject-patient friendly, precise, and inexpensive to perform, should be applicable to studies performed on humans with induced heme oxygenase and studies of effects of therapy for inflammatory and hemolytic diseases. 相似文献
160.
Menno Hoekstra Ronald J. van der Sluis Johan Kuiper Theo J.C. Van Berkel 《The Journal of nutritional biochemistry》2012,23(6):622-628
MicroRNAs modulate processes associated with cell cycle control and differentiation. Here we explored the potential of microRNAs in the modulation of hepatic lipid metabolism and the development of nonalcoholic fatty liver disease.MicroRNA profiles of hepatocytes from low-density lipoprotein (LDL) receptor knockout mice fed a chow diet or a hypertriglyceridemia/fatty liver-inducing Western-type diet (WTD) were determined using quantitative real-time polymerase chain reaction. Ninety-seven of 103 microRNAs measured were expressed by hepatocytes and low variability between hepatocyte pools was observed. Feeding WTD coincided with a marked fivefold decrease in the relative expression level of miR-216 (P<.05) and miR-302a (P<.01). Interestingly, an increased hepatic miR-216 expression was detected in response to fasting. MicroRNA/biological function linkage analysis suggested that the change in hepatocyte microRNA profiles in response to high dietary lipid levels is associated with changes in cell cycle control and proliferation. In accordance with a diminished miR-302a expression on the WTD, hepatocyte mRNA expression levels of miR-302a target genes ABCA1 and in particular ELOVL6 were increased in response to WTD (twofold to ninefold). This suggests a role for miR-302a in hepatic cholesterol, fatty acid and glucose metabolism.In conclusion, we have shown that fatty liver development in LDL receptor knockout mice is associated with a significant change in the hepatocyte microRNA profile, i.e., a fivefold decrease in miR-216 and miR-302a expression. Based upon our comparative gene and microRNA expression studies it is anticipated that miR-302a may prove to be a valuable therapeutic target in the regulation of hepatic fatty acid utilization and insulin resistance. 相似文献