全文获取类型
收费全文 | 457766篇 |
免费 | 51420篇 |
国内免费 | 174篇 |
出版年
2018年 | 4350篇 |
2016年 | 6024篇 |
2015年 | 8197篇 |
2014年 | 9422篇 |
2013年 | 12973篇 |
2012年 | 14765篇 |
2011年 | 14927篇 |
2010年 | 10276篇 |
2009年 | 9540篇 |
2008年 | 13621篇 |
2007年 | 14117篇 |
2006年 | 13172篇 |
2005年 | 12610篇 |
2004年 | 12558篇 |
2003年 | 11688篇 |
2002年 | 11523篇 |
2001年 | 18352篇 |
2000年 | 18358篇 |
1999年 | 14732篇 |
1998年 | 5519篇 |
1997年 | 5724篇 |
1996年 | 5373篇 |
1995年 | 5054篇 |
1994年 | 4892篇 |
1993年 | 4957篇 |
1992年 | 12406篇 |
1991年 | 12116篇 |
1990年 | 11898篇 |
1989年 | 11492篇 |
1988年 | 11007篇 |
1987年 | 10549篇 |
1986年 | 9847篇 |
1985年 | 9803篇 |
1984年 | 8188篇 |
1983年 | 7056篇 |
1982年 | 5452篇 |
1981年 | 4869篇 |
1980年 | 4680篇 |
1979年 | 7720篇 |
1978年 | 6147篇 |
1977年 | 5595篇 |
1976年 | 5386篇 |
1975年 | 5764篇 |
1974年 | 6539篇 |
1973年 | 6384篇 |
1972年 | 5923篇 |
1971年 | 5349篇 |
1970年 | 4731篇 |
1969年 | 4675篇 |
1968年 | 4510篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
101.
Prediction of sequential antigenic regions in proteins 总被引:30,自引:0,他引:30
Prediction of antigenic regions in a protein will be helpful for a rational approach to the synthesis of peptides which may elicit antibodies reactive with the intact protein. Earlier methods are based on the assumption that antigenic regions are primarily hydrophilic regions at the surface of the protein molecule. The method presented here is based on the amino acid composition of known antigenic regions in 20 proteins which is compared with that of 314 proteins [(1978) Atlas of Protein Sequence and Structure, vol. 5, suppl. 3, 363-373]. Antigenicity values were derived from the differences between the two data sets. The method was applied to bovine ribonuclease, the B-subunit of cholera toxin and herpes simplex virus type 1 glycoprotein D. There was a good correlation between the predicted regions and previously determined antigenic regions. 相似文献
102.
Conditions for breaking various medically important yeasts using glass beads, 30 ml Corex centrifuge tubes, and a Vortex mixer were determined. From 75–95% ofCandida hyphal cells and all species of yeasts exceptSporothrix schenckii were broken when 10 g of 0.45–0.50 mm glass beads, 50–300 mg of wet cells in 5 ml of buffer, and 90 s of vortexing were employed. Yeasts ofSporothrix schenckii broke more efficiently when 0.25–0.30 mm beads were used. 相似文献
103.
104.
The time and dose dependence of the relationship between uptake of labelled precursors into protein and RNA and production of testosterone by rabbit follicles was examined. Although testosterone production was stimulated by luteinizing hormone at concentrations between 0.1 and 10 microgram/ml, the uptake of [3H]leucine into protein was significant only when the concentration of luteinizing hormone was greater than 2.5 microgram/ml. Increased production of testosterone was observed within 15 min of stimulation with luteinizing hormone whereas uptake of [3H]leucine was only significant at 90 min. Puromycin (40 microgram/ml) and cycloheximide (10 microgram/ml) in the presence of luteinizing hormone inhibited the synthesis of both testosterone and protein. However, lower concentrations of puromycin (0.1, 1 and 10 microgram/ml) and cycloheximide (1 microgram/ml) had no effect on luteinizing hormone-induced testosterone production but significantly inhibited protein synthesis by 58, 37, 31 and 71%, respectively. Actinomycin D (20, 80 and 160 microgram/ml) alone and in combination with 5 microgram luteinizing hormone/ml severely inhibited uptake of [3H]uridine into RNA without affecting testosterone production. However, with 1 microgram actinomycin/ml, testosterone production was significantly (P less than 0.01) greater than in the presence of luteinizing hormone alone. These results cast doubt on the obligatory role of RNA and protein synthesis in rabbit ovarian follicular steroidogenesis. 相似文献
105.
Properties of a transient current (Icont) believed to reflect a conformational change of the Na-Ca exchanger molecules after Ca2+ binding were investigated. Intracellular Ca2+ concentration jumps in isolated cardiac myocytes were generated with flash photolysis of caged Ca2+ dimethoxynitrophenamine, and membrane currents were simultaneously measured using the whole-cell variant of the patch-clamp technique. A previously unresolved shallow voltage dependence of Icont was revealed after developing an experimental protocol designed to compensate for the photoconsumption of the caged compound. This voltage dependence can be interpreted to reflect the distribution of Na-Ca exchanger conformational states with the Ca2+ binding site exposed to the inside of the cell immediately before the flash. Analysis performed by fitting a Boltzmann distribution to the observed data suggests that under control conditions most exchanger molecules reside in states with the Ca2+ binding site facing the outside of the cell. Dialysis of the cytosol with 3',4'-dichlorobenzamil, an organic inhibitor of the Na-Ca exchange, increased the magnitude of Icont and changed the voltage dependence, consistent with a parallel shift of the charge/voltage curve. This shift may result from intracellular DCB interfering with an Na(+)-binding or Na(+)-translocating step. These observations are consistent with Icont arising from a charge movement mediated by the Na-Ca exchanger molecules after binding of Ca2+. 相似文献
106.
The sensorimotor area of rat cerebral cortex was subjected to repeated electrical stimulation at 10-min intervals, with resultant formation and progressive lengthening of self-sustained after-discharges (SSAD). One and 60 min after the third SSAD ended, we carried out an electron microscopy morphometric analysis of the agranular synaptic vesicles in type I synapses (after Gray) in the second cortical layer of the homotopic area of the unstimulated hemisphere. One minute after the seizure ended, 5.8% enlargement of the synaptic vesicles compared with the control was demonstrated in zone II of the synapse (0.1-0.2 micron from the active zone of the synapse). Neither the size nor the shape of the synaptic vesicles in the other parts of the synaptic apparatus altered. Sixty min after the seizure ended, a 5.5% enlargement of the synaptic vesicles in zone I (0.0-0.1 micron) and a 5.4% enlargement of those in zone II was found. The synaptic vesicles in zone I in the experimental animals were more oval than in the controls. Our findings support the vesicular theory and testify that hyperfunction, up to temporary exhaustion of the synaptic apparatuses, produces a change in the transmitter content of the synaptic vesicles. A raised amount of transmitter in the synaptic vesicles near the active zone could be one of the factors responsible for continued hyperexcitability of the tissue one hour after the seizure had ended. The results likewise support the concept of two mechanisms of synaptic vesicle formation, and hence of the existence of two different vesicle populations. 相似文献
107.
108.
109.
Minh C. Nguyen Guang Huan Tu Kathryn E. Koprivnikar Melissa Gonzalez-Edick Karin U. Jooss Thomas C. Harding 《Cancer immunology, immunotherapy : CII》2010,59(9):1313-1323
A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that
may be related to immunotherapy potency. In this study, protein microarrays containing >8,000 human proteins were screened
with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte–macrophage colony-stimulating factor (GM-CSF)-secreting whole cell immunotherapy.
Thirty-three proteins were identified that displayed significantly elevated (P ≤ 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis,
galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis
of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly
correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence
following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1
was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody
induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in
prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived
antibody responses. 相似文献
110.
Binomial parameters of transmitter secretion were calculated on the basis of analysis of synaptic potentials in the frog sartorius muscle. Negative values of the parameter p were found in some synapses. This happened most often in low Ca2+ concentrations and with low amplitude of miniature end-plate potentials. The results were interpreted in terms of a model assuming spatial heterogeneity of probability of transmitter quantum release at different release points. Simulation of transmitter secretion by computer showed that the appearance of negative values of the parameter p and incorrect estimates of n experimentally are connected with the form of distribution of probability of transmitter quantum release in the synapse and with the amplitude of miniature potentials.S. V. Kurashov Kazan' Medical Institute, Ministry of Health of the RSFSR. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 182–189, March–April, 1984. 相似文献